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THE INFLUENCE OF INSULIN

ON PROTEIN METABOLISM

Since various opinions have been expressed about thepart played by insulin in protein metabolism, it is fittingto review some of the literature to see how these dif-ferent conclusions may be explained. Table i presentsa summary of selected articles of which some are oldand often quoted, and others permit one to think of themost recent methods and results in this field. The tableindicates some of the main headings although no suchsimplified arrangement does justice to such a varietyof experimental detail.

It is clear that the exaggerated protein metabolismof pancreatectomy or severe diabetes mellitus and thecontrol of this accelerated protein catabolism by insulinhave been consistently observed1"5 since the epoch-making works of von Mering and Minkowski0 andBanting and Best7. There is no question about the factthat, when used to replace severe insulin deficiency,insulin has a powerful protein anabolic action withincertain limits. "Within limits" means that protein me*tabolism is restored to normal, but that (except for thetransitory restoration of the protein deficit) there is nosustained anabolism above and beyond the normal levelof protein balance.

In contrast to the depancreatized animal, the resultsin Houssay animals may be noted. The actual fastingnitrogen excretion is the same in the normal animal andin the Houssay animal which lacks both pituitary andpantreas. One would conclude from this that insulindoes not influence protein metabolism in any primaryor direct manner, a conclusion which would be quite atvariance with the striking effect of insulin in the diabeticanimal. Both phenomena force one to think of themetabolic situation in which insulin is acting. In anycase, the tendency of insulin to restore the protein bal-ance of diabetic animals to, but not beyond, the normalequilibrium has been further examined by the use of

insulin in normal animals and man. It is here, i.e., inthe normal animal, that some difference of opinion hasarisen. Without analyzing all of the experiments, onemay note certain features of the experiments listed inTable i under the heading, "Investigators who failed toobserve protein anabolism."

In the first place, some of these experiments wereconducted in fasted animals. There seems to be com-plete agreement that the administration of insulin doesnot cause demonstrable protein anabolism in the fastedanimal lf 8> 9> 10. This is compatible with other observa-tions on protein anabolism. Thus, Munro11 reviews thecaloric requirements for protein storage under variousconditions and concludes that the addition of extraenergy to an adequate diet usually leads to nitrogenretention whether this energy is provided by carbo-hydrate or fat. Moreover, the feeding of carbohydrate tofasting animals reduces the nitrogen output, but thefeeding of fat does not have this effect until the fatstores are exhausted. If these things are so in normalanimals with ample endogenous insulin, one would notexpect protein anabolism to take place when insulin wasadded during the fasting state. Even insulin cannot makebricks without straw. These comments on protein me-tabolism during fasting may be concluded by notingan important difference between insulin and growthhormone. Growth hormone has a nitrogen sparing ac-tion in the fasting normal animal12'13. With this effecton protein there is a mobilization of fat, which is mani-fested by increased ketonuria and also14'15 by a diminu-tion in body fat.

Another point about these experiments (Table I, II,A) is that in some of them9'16> 17 one dose of regularinsulin was given daily, sometimes followed by theobservation of urinary nitrogen for a few hours only.It now seems, from many studies on nitrogen excretion,from studies with repeated doses of insulin or protamineinsulin, and from current knowledge of the cumulativeaction of growth hormone18'19 that the conditions whichlead to protein anabolism are the ones in which there

NOVEMBER-DECEMBER, 19 5 3 4 9 1

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TABLE 1

Selected studies of the influence of insulinon protein metabolism

I. Pancreatectomy results in an increased catabolism ofendogenous protein (increased N excretion duringfasting)6.Insulin treatment of depancreatized animal, or of severediabetic patient, prevents this "secondary" accelerationof protein catabolism1-5.

II. Insulin given to normal animalsA. Investigators who failed to observe protein anabo-

lism:No increased growth of rabbits16.No effect on fasting N balance of rats8.No effect on growth or N excretion of normal rats,with or without control of diet9.No change or an increase in N excretion17.Increased N excretion of fasting dogs1.No effect on growth of rats25"27.No effect on protein depletion or repletion10.

B. Investigators who concluded that insulin promotesprotein anabolism:Glucose and insulin spare more protein than glu-cose alone in normal subjects20.Insulin causes positive N balance in fed normaldogs1.Insulin causes nitrogen retention in normal rats,with or without constant diet21.Positive N balance in patients given insulin (appe-tite increased)22.Insulin reduces accumulation of blood NPN innephrectomized dogs23.Liver and diaphragm incorporate more labeled ami-no acid under influence of insulin if glucose is pres-ent2*.

III. Relation of insulin to the action of other hormones onprotein metabolismA. Testosterone (T)

No effect of T on blood NPN in depancreatizeddogs29.Anabolic effect of T occurs in alloxan diabetic rat50.Ability of T to increase arginase activity of kidneywas not impaired in alloxan diabetes31.T causes N retention in hypophysectomized rats onconstant diet32.33.

B. Growth Hormone (GH)Action is impaired in insulin deficiency34.Nitrogen retention in fasting rats12'13.Lability of nitrogen of different muscles varies underinfluence of GH or inanition45.Effect of GH on special tissues46.Part of defective growth of hypophysectomized ratswas restored by forced feeding38.GH caused N retention in diabetic rats, but no Nretention in Houssay cats35-37.Insulin causes growth in hypophysectomized rats28.Extended protein repletion in rats10.

C. Adrenal Cortical HormonesEffect of cortisone on protein of different tissues47.Insulin does not prevent the increased N excretioncaused by cortisone or ACTH40-41.Increased insulin seemed to prevent or reduce in-creased N excretion in diabetics receiving ACTH42.

D. Excess catabolism of hyperthyroidism and growthpromoting action of thyroid hormone in cretinismboth occur in presence of ample insulin (the thy-roid is not discussed herein).

is a fairly sustained action of the anabolic influence.The next group of experiments (Table I, II, B) pro-

vides definite evidence that in the fed animal or man,insulin tends to cause protein anabolism as measuredby nitrogen balance1'20> 21> 22 or by other methods23,24 i^g tendency of insulin to produce a positivenitrogen balance has not led to growth in normal ani-mals25"27 and with the exception of the report of Salterand Best28 which will be discussed later, there is noevidence that insulin influences growth as shown by thetibia test. Probably the physician has seen the moststriking failure of insulin to produce growth in thecase of patients with islet cell adenomas. Some of thesepeople have had hypoglycemia for years before opera-tion; some are thin, many slightly obese; but none haveever had excessive growth of the type seen in acrom-egaly. Whatever the reason for this may be, these patientsshow us that the anabolic influence of insulin does notof itself suffice for body growth, however important itmay be as a synergist to growth hormone.

It is probable that a study of the relation of insulinto the action of other hormones which promote proteinanabolism is essential to an understanding of the actionof insulin itself (Table I, III). In the case of testoster-one, more information is required to define its relationto other anabolic agents. The evidence of Sirek andBest29 indicates that insulin is required for the anabolicaction of testosterone, since there was no alteration ofthe blood NPN by testosterone in depancreatized dogsdeprived of insulin. The studies of Kochakian30'31 donot contradict this because the presence of insulin is notexcluded by our present methods of producing diabetesin rats. For the moment, one must conclude that thepresence of insulin, but not necessarily its increasedsecretion, is required for the action of testosterone onprotein metabolism. In contrast to this, testosteronecauses nitrogen retention in the absence of growth hor-mone, i.e., in the hypophysectomized animal32.33. Al-though this is a concise statement, the biochemical sitesof action of all hormones which regulate protein me-tabolism are quite obscure.

The relation of insulin to anterior pituitary growthhormone has been studied for years by the use of crudeand later of highly purified preparations with growth-promoting activity. Thus, it has been determined thatin depancreatized dogs and cats maintained on fixeddoses of insulin, the action of growth hormone onnitrogen balance is present but greatly reduced34' 35.Nitrogen retention also takes place when growth hor-mone is given to alloxan diabetic rats whose available

4 9 2 DIABETES, VOL. 2, NO. 6

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insulin is obviously reduced36' 37. More recently, theeffect of one hormone in the absence of the other hasbeen examined. Milman et al.35, using metabolic periodsin hypophysectomized-depancreatized (Houssay) catsfound that in the absence of insulin, growth hormonecaused no retention of nitrogen. Since growth hormoneis most accurately tested in hypophysectomized animals,this result cannot be due to the pituitary deficiency, andthe essential part played by insulin in the anabolic actionof growth hormone is apparent.

On the other hand, the determination of the effectof insulin on protein metabolism in the absence ofgrowth hormone is only beginning to receive attention.The absence of growth hormone means the use of thehypophysectomized animal which, as is well known,is extremely sensitive to insulin. Nevertheless, Salter andBest28 have described growth in hypophysectomizedrats treated with protamine insulin. The tendency ofhypophysectomized rats to continue growing up to 40days of age was duly controlled. Growth was measuredby body weight, body length and the tibia test, andthere is no doubt about the fact that growth occurred.However, there is still doubt about the mechanism bywhich this growth was produced. The impaired growthafter hypophysectomy is observed in the presence ofample insulin and of insulin sensitivity but on a re-duced food intake. The protamine insulin which was usedincreased the appetite of the treated rats which werealso given additional food or glucose to prevent or treatinsulin reactions. Samuels et al.38 restored part of thedefective growth of hypophysectomized rats by forcedfeeding. For this reason it is uncertain whether theresults of Salter and Best28 were due to some primaryaction of insulin or to the secondary effect of the in-creased food intake.

During the past year Doctor McCann and I have donepreliminary experiments related to this problem. On aconstant diet of meat, the nitrogen excretion of catswas recorded. When 5 to 10 grams of glucose were added

TABLE 2The effect of operative procedures on

pancreatic diabetes in the cat39

Type and No.of Cats

Normal (7)Depancreatized (10)Hypox-depan. (6)Adrex-depan. (14)

Glucose Nitrogen

Urine Liverfatty

Ketones acidsg/k/d* g/k/d* mg/k/d* per cent

0 0.6 15 53.2 1.4 133 240.7 0.7 8 90.5 0.7 10 7

* Fasting values—gm. or mg. per kilo per day.

NOVEMBER-DECEMBER, 1953

daily to the meat diet, the usual protein sparing action ofcarbohydrate was observed, as nitrogen retention, in thenormal animals (Tables 2 and 3). In hypophysectomizedcats treated in a similar manner, there was no proteinsparing effect of carbohydrate. These experiments weredesigned to test the effect of the endogenous insulinwhich is presumably secreted in response to the addedglucose and, at the same time, to avoid the hazard ofinsulin reaction. The results in cats differ from those inrats in which Bancroft, Geiger and Hagerty37 found thatthe nitrogen sparing action of sugar was of the samemagnitude in normal and in hypophysectomized animals.This indicates that one must reckon with a strikingspecies difference in such experiments.

HYPOX.-DEPAN.

0 2 0INSULIN

FIGURE I. Cat 6-53. Hypophysectomized March 4; depan-creatized, April 6, 1953. Diet of 50 gm. of meatand pancreatic extract (Viokase) was constantthroughout the periods charted. These periods wereconsecutive and consisted of a control period of 5days, a middle period of 5 days when 2 units ofprotamine insulin was given daily, and an after-period of 4 days without insulin. The effect ofinsulin on the glycosuria is obvious; the effect onthe nitrogen excretion is significant. The differencebetween the nitrogen excretion of the second con-trol period and the insulin period is 0.38 gm. perday. This corresponds to the average nitrogen re-tention observed when 5 gm. of glucose was addedto the diet of the normal cat (cf. Table 3).

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TABLE 3Protein sparing action of carbohydrate in cats

CatsType

NormalHypox.

No.

105

Average Urinary Nitrogen

Meat*only

gm/day3.55+0.112.89 + 0.26

Meatplus

glucosegm/day 1

3.16+0.132.97+0.26

Averagenitrogenretainedrm gm/day

—0.39+0.06+0.08+0.12

1 The amount of meat (100 gm. daily) was constantthroughout all periods.

We have tested the effect of insulin in a singleHoussay animal (Figure i ) . Compared to controlperiods before and afterward on a constant diet, insulinbrought about the utilization of 5 gm. of urinaryglucose. This was accompanied by a significant diminu-tion in nitrogen excretion. If this single experiment isconfirmed, the situation will be as follows. Glucosespares protein in the normal cat; glucose fails to spareprotein in the hypophysectomized cat; glucose utilizedby administered insulin spares protein in the Houssayanimal. This means that glucose and insulin may ormay not spare protein when the pituitary is absent.Such a result suggests that better methods of assayare needed.

Little is known of the relation between insulin andthe adrenal cortical hormones, yet this is a large com-ponent of the subject of insulin and protein metabol-ism. Long and Lukens39 showed that adrenalectomyabolished the protein catabolic response to pancreatec-tomy and many investigators (e.g.40'41) have demon-strated the protein catabolic action of ACTH and cortisoneunder various conditions. However, the effect of insulinon the protein catabolic action of the adrenal corticalhormones has received less attention. Ingle et al.A0

and Conn et al.iX found that in the rat and in manlarge doses of insulin which reduced the glycosuria didnot control the increased nitrogen excretion producedby cortisone or ACTH. On the other hand, increaseddoses of insulin appeared to prevent or reduce theincreased N excretion in diabetic patients who werereceiving ACTH42 but here the picture is complicatedby the simultaneous relief of the complicating rheu-matic disease. All these possibilities are well discussedin the study of Burns et al.i9 who found that cortisonedid not alter the response to insulin in the fasting statebut strikingly altered the glucose-insulin test.

The failure of insulin to produce growth in normalanimals or in patients with islet cell tumors might bedue to the antagonistic action of the adrenals. If thiswere so, it might explain why, in spite of these re-

494

suits in the normal animal, Salter and Best28 observedgrowth in their hypophysectomized rats which lackedthe normal degree of adrenal cortical function.

It is- with an eye to the future that certain studieson protein metabolism should be particularly noted.The importance of the quantity and quality of theprotein intake, the relation between caloric intake andprotein storage and the need for differentiating theeffects of the anabolic hormones which may be actingsimultaneously are fairly well recognized. In addition,there are features of protein metabolism which maypoint the way to the development of better methods.

The procedures most commonly used to study pro-tein metabolism have included the measurement ofdietary, urinary and fecal nitrogen; body growth;changes in the protein or nitrogen content of thecarcass; changes in the rate of accumulation of thenitrogenous constituents of the blood * in nephrec-tomized animals. All of these record the systemicequilibrium or response and all are affected by bothdietary and hormonal factors. If, in agreement withHandler50, one calls growth hormone, testosterone,thyroxine and insulin the anabolic hormones, it is al-ready clear that they act in different ways even ifconsiderable synergism is involved. How are we toidentify more accurately these sites of action on pro-tein metabolism? First, we should make more use ofthe response of individual tissues with the hope ofselecting the most significant site of action of themetabolic hormones. In 1936, Addis, Poo and Lew43

examined the rate of protein formation in numeroustissues of the body after depletion and re-feeding.They concluded that, "each organ and tissue has itsown individual characteristics with respect to the de-gree and rate of the rebuilding of protein when caseinis given after a period of protein loss" (see Figure2) and recorded appropriate details. Munro and Nai-smith44 have made similar observations relevant tothe influence of energy intake on protein metabolism,and they call attention to "the bodily distribution ofchanges in nitrogen balance." Geiger et al.i5 foundno effect of insulin, growth hormone or cortisone onthe gain in body weight during repletion.

This provides an interesting background to thecurrent reports of Greenbaum and Young46 and Scow47.The former46 compared the loss of nitrogen in varioustissues during inanition and the gain in tissue nitrogenduring treatment with purified growth hormone. Inparticular, the striking lability of the nitrogen contentof certain muscles and the relative stability of other

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+60%

+40%

+20%

-20%10 12 J4Z 4 6 6

DAYSFIGURE 2. Changes in protein content from levels at 7

day fast. From: Addis, Poo and Lew: J. BiolChem. 116:343, 1936

muscles was noted. Scow47 observed the effect of growthhormone on various protein fractions in the musclesof thyroidectomized and hypophysectomized rats. Asan example of his results, growth hormone promoteda marked weight increase in the thigh muscle, ac-companied by a significant increase in the myosinfraction. This agrees with Greenbaum and Young's46

finding that the quadriceps was a most active and"labile" muscle in regard to changing its nitrogencontent. The individual characteristics of different tis-sues has also been demonstrated in the response ofrats to cortisone which caused a wastage of nitrogenfrom carcass fractions other than structural protein (i.e.collagen and elastin)48. The protein of the liver wasincreased by this so-called catabolic hormone, indicat-ing that a -re-distribution of protein may take placewithin the overall protein balance. The sites andnature of protein anabolism induced by testosteronehave also been described49. In summary, if the tissuesand the particular proteins which are influenced by thehormones can be identified, there should be bettermethods of assaying their action.

SUMMARY

Insulin promotes protein anabolism secondarily byits action on the utilization of carbohydrate in thepresence of other anabolic hormones. The followingfacts appear to support this concept.

(a) Insulin does not cause nitrogen retention inthe fasting animal (in contrast to growth hormone).

(b) The protein sparing power of carbohydrate.(c) The quantitative relations between caloric in-

NOVEMBER-DECEMBER, 195 3

take and protein anabolism in normal animals.(d) Additional insulin, administered or from a

secreting islet cell tumor, does not cause growth, inspite of a definite tendency to nitrogen retention.

(e) Insulin, as replacement therapy, prevents orimproves diabetic dwarfism and prevents the catabolicresponse to pancreatectomy.

(f) Since the protein catabolic response of pan-creatic diabetes is abolished by removing the pituitaryor adrenal glands to the same degree as when insulinis given, insulin would not appear to have a primaryor direct action on protein metabolism.

(g) As noted, in all of these conditions otheranabolic hormones, notably growth hormone, are pre-sent.

(h) The failure of normal growth in the hypophy*sectomized animal takes place in the presence ofendogenous insulin which may cause added fat forma-tion. It is in part corrected by forced feeding. Suchadded factors as age and possibly species which in-fluence the degree to which hypophysectomized animaismay grow, must be considered.

Possibly discrepant facts are: (1) the administra-tion of insulin causes true growth in rats (certainquestions of diet and species behavior may needelucidation) and (2) the nitrogen retaining effectof insulin in the Houssay animal (one experimentonly).

In conclusion, a review of these studies on the in-fluence of insulin in protein metabolism suggests thatwe should examine the effects of anabolic hormoneson specific tissues, on particular proteins of thosetissues and probably on the accelerated incorporationof labelled amino acids into such selected proteins inthe hope of improving methods of assay which atpresent permit considerable discrepancies to appear.

FRANCIS D. W. LUKENS, M.D.

From the George S. Cox Medical Research Institute, Uni-versity of Pennsylvania, Philadelphia, Pa.

REFERENCES

1 Sokhey, S. S. and Allan, F. N.: The relationship ofphosphates to carbohydrate metabolism. I. Time relationshipof the changes in phosphate excretion caused by insulin andsugar, Biochem. J. 18:1170-1184, 1924.

2 Falkenhausen, M. F. von: Untersuchungen iiber denEmeissstoffwechsel beim experimentellen Pankreasdiabetes,Arch. f. exper. Path. u. Pharmakol. 109:249-275, 1925.

3 Lauter, S. and Jenke, M.: Uber den Eiweissstoflwechselbei verschiedenen Krankheiten (Versuche iiber das N-mini-mum bei Diabetes, Carcinom, Leukamie, Bestrahlung, Thy-

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EDITORIALS

reotoxikose (Basedow), (Pneumonie), D. Arch. klin. Med.146:323-345, 1925.

4 Atchley, D. W., Loeb, R. F., Richards, D. W., Benedict,E. M. and Driscoll, M. E.: On diabetic acidosis—a detailedstudy of electrolyte balances following the withdrawal andre-establishment of insulin therapy, J. Clin. Investigation12:297-326, 1933.

5 Chaikoff, I. L. and Forker, L. L.: The antidiabetic actionof insulin on nitrogen metabolism, Endocrinology, 46:319-326, 1950.

6 Mering, J. von and Minkowski, O.: Diabetes Mellitusnach Pankreasextirpation, Arch. f. exper. Path. u. Pharmakol.26:371, 1889.

7 Banting, F. G. and Best, C. H.: Internal secretion ofpancreas, J. Lab. & Clin. Med. 7:251-266, 1922.

8 Bonnet, R.: Regulators of nitrogen metabolism. 4.Insulin. Trav. membres soc. chim. biol. 23:1515-34, 1941(in Diabetes Abstracts 6:51, 1947).

9 Goldblatt, M. W. and Ellis, R. W. B.: Effect of insulinon growth, nitrogen excretion and respiratory metabolism,Biochem. J. 25:221-235, 1931.

1 0 Geiger, E., Ershoff, B. H., Wasserman, L. and El Rawi,I.: Effect of hormone therapy on body weight during proteindepletion and repletion, Proc. Soc. Exper, Biol. & Med.82:629-633, 1953.

1 1 Munro, H. N.: Carbohydrate and fat as factors inprotein utilization and metabolism, Physiol. Rev. 31:449-489,1951.

12 Harrison, H. C. and Long, C. N. H.: Effects of anteriorpituitary extracts in the fasted Rat, Endocrinology 26:971-978,1940.

1 3 Bennett, L. L., Kreiss, R. E., Li, C. H. and Evans, H. M.:Production of ketosis by the growth and adrenocorticotropichormones, Am. J. Physiol. 152:210-215, 1948.

14 Lee, M. O. and Schaffer, N . K.: Anterior pituitarygrowth hormone and composition of growth, J. Nutrition7:337-363, 1934-

15 Li, C. H., Simpson, M. E. and Evans, H. M.: Influenceof growth and adrenocorticotropic hormones on the bodycomposition of hypophysectomized Rats, Endocrinology 44:71-

75, 1949-16 Long, M. L. and Bischoff, F.: The effect of insulin upon

the body weight of the rabbit, J. Nutrition 2:245-249, 1930.17 Jakobson, B. M. and Reinwein, H. : Untersuchungen

iiber die Wirkung des Insulins und Adrenalins auf dieStickstoff—und Schwefelausscheidung, Arch. f. exper. Path,u. Pharmakol. 170:84, 1933.

18 Gaebler, O. H., Bartlett, P. D. and Sweeney, M. J.:Remarkable effectiveness of small daily doses of growth hor-mone in dogs, Am. J. Physiol. 165:486-490, 1951.

1 9 de Bodo, R. C , Kurtz, M., Ancowitz, A. and Kiang,S. P. : Anti-insulin and diabetogenic actions of purified an-terior pituitary growth hormone, Am. J. Physiol. 163:310-318, 1950.

20 Janney, N . W . and Shapiro, I.: The role of insulin inprotein metabolism, Arch. Int. Med. 38:96-108, 1926.

2 1 MacKay, E. M., Barnes, R. H. and Bergman, H. C :Influence of insulin on protein metabolism as measured bynitrogen balance, Am. J. Physiol. 126:155-157, 1939.

22 Kountz, W . B., Ackermann, P. G. and Kheim, T.: Theinfluence of some hormonal substances on the nitrogen bal-

496

ance and clinical state of elderly patients, J. Clin. EndocrinoL13 =534-547, 1953-

2 3 Mirsky, I. A . : The influence of insulin on the protein

metabolism of nephrectomized dogs, Am. J. Physiol. 124:569-

575, 1938.2 4 Krahl , M. E. : Hormones and the metabolism of isolated

tissues, Diabetes 2 :26-30, 1953.2 5 Ferrill, H . W . : The effect of daily administration of

insulin on growth of the white rat, Growth 5 :119-121, 1941.2 6 Ingle, D . J., Evans, J. S. and Sheppard, R.: The effect

of insulin on the urinary excretion of sodium, chloride,

nitrogen and glucose in normal rats, Endocrinology 35:370-

379. 1944.2 7 Ingle, D . J . and Nezamis, J . E.: The effect of insulin

on the tolerance of normal male rats to the overfeeding of a

high carbohydrate diet, Endocrinology 40:353-357, 1947.2 8 Salter, J. and Best, C. H . : Insulin as a growth hormone,

Federation Proc. 12:122, 1953.2 9 Sirek, O. V. and Best, C. H . : The protein anabolic

effect of testosterone propionate and its relationship to in-

sulin, Endocrinology 52:390-395, 1953.3 0 Wright , P. M. and Kochakian, C. D . : Metabolic effects

•of testosterone propionate in experimental diabetes, Am. J .

Physiol. 173:217-222, 1953.8 1 Kochakian, C. D., Wright , P. M. and Robertson, E.:

Testosterone propionate and arginase activity in diabetic

rats, Arch. Biochem. 36:221-230, 1952.? 2 Kochakian, C. D., Stettner, C. E., Clancy, K., Abbott,

C. and Moe, J . : Comparison of protein anabolic properties

of testosterone propionate and growth hormone in the rat,

A.m. J. Physiol. 160:66-74, 1950.3 3 Rupp, J. J. and Paschkis, K. E.: Influence of testosterone

propionate on the protein metabolism of hypophysectomized

Rats, Metabolism 2:268-270, 1953.3 4 Gaebler, O. H. and Robinson, A. R.: Effects of the pan-

creas and the adrenals upon production of nitrogen storage

with pituitary preparations, Endocrinology 30:627-634, 1942.3 5 Milman, A. E., D e Moor, P. and Lukens, F. D . W . :

Relation of purified growth hormone and insulin in regula-

tion of nitrogen balance, Am. J. Physiol. 166:354-363, 1951.3 6 Bennett, L. L. and Laundrie, B. : Effects of the pituitary

growth and adrenocorticotropic hormones on the urinary

glucose, nitrogen and ketone bodies of diabetic cats main-

tained on a carbohydrate-free diet, Am. J. Physiol. 155:18-23,

1948.3 7 Bancroft, R. W. , Geiger, E. and Hagerty, E. B. : Nitrogen-

sparing effect of carbohydrate related to t ime factor with

hypophysectomized and diabetic rats, Endocrinology 49:149-

153, 1951-s s Samuels, L. T., Reinecke, R. M. and Bauman, K. L.:

Growth and metabolism of young hypophysectomized rats fed

by stomach tube, Endocrinology 33:87-95, 1943.3 9 Long, C. N . H . and Lukens, F. D . W . : The effects of

adrenalectomy and hypophysectomy upon experimental diabetes

in the cat, J. Exper. Med. 631465-490, 1936.4 0 Ingle, D. J., Sheppard, R., Evans, J. S. and Kuizenga,

M. H.: A comparison of adrenal steroid diabetes and pancreaticdiabetes in the rat, Endocrinology 37:341-356, 1945.

4 1 Conn, J. W., Louis, L. H. and Johnston, M. W. : Metab-olism of uric acid, glutathione and nitrogen and excretion of"11-oxysteroids" and 17-ketosteroids during induction of dia-

DIABETES, VOL. 2, NO. 6

BDITORIALS

betes in man with pituitary adrenocorticotropic hormone, J. Lab.& Clin. Med. 34:255-269, 1949.

4 2 Brown, E. M., Jr., Lukens, F. D. W. , Elkinton, J . R. andDe Moor, P. : Observations on the metabolic and antiarthriticeffects of ACTH and cortisone in diabetics, J. Clin. Endocrinol.11:1363-1374, 1950.

4 3 Addis, T., Poo, L. J. and Lew, W . : The rate of proteinformation in the organs and tissues of the body. I. After caseinrefeeding, J. Biol. Chem. 716:343-352, 1936.

44 Munro, H. N . and Naismith, D . J. : The influence ofenergy intake on protein metabolism, Biochem. J. 54 :191 -

197, 1953-45 Greenbaum, A. L. and Young, F. G.: A comparison of

the differences in the total nitrogen content of the muscles ofthe rat resulting from treatment with growth hormone andfrom inanition, J. Endocrinol. 9:127-155, 1953.

4 6 Scow, R. O. : Effect of growth hormone on various pro-tein fractions in striated muscle of thyroidectomized and hypo-physectomized rats, Am. J. Physiol. 773:199-206, 1953.

4 7 Silber, R. H. and Porter, C. C : Nitrogen balance, liverprotein repletion and body composition of cortisone treatedrats, Endocrinology 52:518-525, 1953.

48 Kochakian, C. D., Robertson, E. and Bartlett, M. N . : Sitesand nature of protein anabolism stimulated by testosteronepropionate in the rat, Am. J. Physiol. 163:332-346, 1950.

4 9 Burns, T. W., Engel, F. L., Viau, A., Scott, J. L., Jr., Hol-lingsworth, D. R. and Werk, E.: Studies on the interdependenteffects of stress and the adrenal cortex on carbohydrate metab-olism in man, J. Clin. Investigation 32:781-791, 1953.

50 Handler, P . : Protein as a metabolic fuel, in Major Me-tabolic Fuels, Brookhaven Symposia in Biology, No. 5, Pp. 99-122, 1953.

NUTRITIONAL ADEQUACY OF THE DIABETIC DIET

Advances in medicine have enabled the physician to re-duce the mortality rate from diabetes mellitus. The in-troduction of insulin therapy, the understanding of fluidand electrolyte balance in the treatment of ketotic acid-otic coma and the use of sulfa drugs and antibioticswere the contributing factors to this increased longevity.One of the major problems that remains is the avoidanceof chronic invalidism of those whose lives have beenextended. The treatment of a chronic disease should bedesigned to allow the individual to make his full contri-bution to society. The mere prolongation of life withouthealth or happiness is short of the desired goal.

In the maintenance of good health and a sense of well-being, the adequacy of the nutrition of the individual isa very important factor. The term "adequate" is relativeand its interpretation very variable. A diet adequate fora healthy young, vigorous adult male is excessive for afemale or an elderly male. At the same time, it may beinadequate for a growing boy or in the rehabilitationconvalescent period of the young adult. The problem isto define a set of nutritional requirements for the dia-betic and teach the physician to calculate the diets ac-cordingly.

A great many dietary standards have been promulgatedfor population groups and even for individuals. In 1940the Food and Nutrition Board of the National ResearchCouncil accepted the responsibility for developing adietary standard for the people of the United States. Thephilosophy of their recommendations was based on al-lowances suitable for the achievement of good nutritionin the whole population rather than filling the minimalneeds of the average individual. These were published in

1943, and revised in 1945 and again in 1948. They areat present undergoing further revisions in certain detail.

It is universally accepted that diet therapy is the key-stone to modern treatment of diabetes mellitus. The ac-cent of the diet therapy has been on the control of onevery obvious phase of the condition, that is carbohydrateutilization and prevention of hyperglycemia and glyco-suria. This emphasis at times has distracted attentionfrom the over-all nutritional adequacy of the diet. In thepublished literature in this field, frequent reference ismade in the text of an article to the importance of nu-trition. Examination of the tables and figures of dietsactually prescribed not infrequently fail to substantiatethe text. The statement, "If the weight is maintained, thediet is adequate in calories," is commonly quoted. Ananalysis of this statement proves its incompleteness. Thestatement should read "If the ideal or optimum weight ismaintained, the diet is adequate in calories." Reducedcaloric intakes result in adaptative mechanisms withassociated lowering of metabolic requirements and slow-ing down of metabolic processes. Caloric equilibriumcan be reached and body weight maintained at a 1200to 1500-caloric intake for a young adult whose optimumcalorie requirement may be 2600 calories. At the lowerequilibrium, he is incapable of a full active, healthy lifeand will show easy fatigibility, decreased resistance toinfection, loss of vigor, and even apathy and mental de-pression. At the higher level of a caloric equilibra-tion, he can be a normal adult with a sense of well-being.

The most commonly prescribed diets for diabeticadults today (Table 1) provide approximately 1600 to2100 calories.

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