11. Integration of Metabolism New Version 2

8/21/2019 11. Integration of Metabolism New Version 2

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INTEGRATION OF METABOLISM

Questions:

1. What is normal loo! su"ar le#el$ %es&rie the me&hanisms an! 'a&tors

that re"ulate loo! su"ar le#el. A!! a note on insulin !e(&ien&). * A+ril

,-. What is normal loo! "lu&ose le#el$ Write in !etail aout its re"ulation.*

Mar&h //0. Write in !etail aout "lu&ose haemostasis in the human or"anism an!

a!! a note on its iome!i&al im+ortan&e. * O&t //0. What are the normal 'astin" an! +ost +ran!ial loo! "lu&ose le#els$

E2+lain ho3 normal loo! "lu&ose le#el is maintaine!. A!! a note on the

!isru+tion o' hormonal re"ulation o' Bloo! "lu&ose. * Au" //44. Short notes: Inter+retation o' "lu&ose toleran&e test. *O&t 1,,-

REG5LATION OF BLOO% GL56OSE

1. The human body functions as one community. Communication between tissues is

mediated by the nervous system, by the availability of circulating substrates and byvariation in the levels of plasma hormones

. The integration of energy metabolism is controlled primarily by the action of

hormones, including insulin, glucagon and catecholamines (epinephrine and nor

epinephrine).

0. The four maor organs important in fuel metabolism are liver, adipose tissue

mus&le an! rain.

. Normal #alues:!. "asting plasma glucose levels# 70$!!0 mg%dl2. &ost prandial# ' !0 mg%dl. &lasma value is slightly higher than whole blood glucose because of *+Cs

with less water

. rine contains no glucose up to plasma level of !-0 mg%dl this is called renalthreshold

4. Fa&tors maintainin" hi"h "lu&ose in loo!:1. Asor+tion 'rom intestines# The dietary carbohydrates are digested and

absorbed as monosaccharides (glucose, fructose, galactose etc.). The liver

converts fructose and galactose into glucose.. Gl)&o"enol)sis# /egradation of glycogen in liver produces free glucose due

to limited amount glycogen in liver. This can maintain glucose only upto

hours of fasting.0. Glu&oneo"enesis# The degradation of glycogen in muscle results in the

formation of lactate. +readown of fat in adipose tissue will produce free

glycerol and propionate. 1actate, glycerol, propionate and some amino acids

are precursors for gluconeogenesis that actively occurs in liver and idney.luconeogenesis continuously adds glucose to the blood. Cori cycle is

responsible for the conversion of muscle lactate to glucose in liver.. 7i!ne): Glucose is continuously 3ltered by the glomeruli, reabsorbed and

returned to the blood. lf the level of glucose in bfood is above !40$!-0 m%dl,

glucose is e5creted in urine (glycosuria) This value (!40$!-0 mg%dl) is referred

to as renal threshold for glucose.4. Glu&a"on: in&reases "lu&ose le#el

8. Fa&tors &ausin" !e+letion:


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1. Tissue utili6ation# about two$thirds of the blood glucose is utili6ed by the

brain. The remaining one third by *+C and seletal muscle.. lycogen synthesis0. lucose converted to fat. nsulin

4. 9ost +ran!ial re"ulation:!. 8fter a meal blood glucose level increases which stimulates insulin secretion

by beta cells of pancreas2. nsulin facilitates entry of glucose to cells e5cept brain for utili6ation. nsulin helps conversion of e5tra glucose to glycogen and fat

8. Re"ulation in 'astin" state:!. 2 to 29 hours after a meal, the blood glucose level falls to near fasting levels.

(-0 mg%dl). t may go down further but this is prevented by following

processes#2. "irst hours# hepatic glycogenolysis increases blood glucose. Continued fasting# luconeogenesis will tae charge of maintaining glucose

level.. lucagon, epinephrine, glucocorticoids, growth hormone, 8CT:, and Thyro5in

act as hyperglycaemic hormones.

. ;ormone re"ulations o' "luo&se# &rimarily, insulin lowers blood glucose level

(hypoglycemic) while the rest of the hormones oppose the actions of insuiln

(hyperglycemia)!) Insulin#

a. lnsulin is produced by +$cells of the islets of 1angerhans in response to

hyperglycemia.b. t lowers blood glucose t favours glycogenesisc. t promotes lycolysis t inhibits luconeogenesis

2) Glu&a"on#a. lucagon is synthesi6ed by a$cells of the islets of 1angerhans of the

pancreas. :ypoglycemia stimulates its production.b. lucagon is basically involved in elevating blood glucose

concentration. lt enhances gluconeogenesis and glycogenolysis.) Glu&o&orti&oi!s#

a. These hormones are produced by adrenal corte5. lucocorticoids

stimulate protein metabolism and increase gluconeogenesis (increase


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the activities of en6ymes$glucose 4$phosphatase and fructose !,4$

bisphosphatase).b. The glucose utili6ation by e5trahepatic tissues is inhibited by

glucocorticoids. The overall e


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. nsulin$secreting pancreatic tumour

. 8lcohol induced hypoglycaemia often lined with etoacidosis

=. 8limentary (rapid eunal emptying with e5aggerated insulin response) 8fter

gastrectomy dumping syndrome or bowel bypass surgery or resection

4. 8cDuired adrenal insuEciency

7. 8cDuired hypopituitarism-. /etermination glucose#

!. lucose o5idase method#2. t converts glucose to gluconic acid and hydrogen pero5ide. &ero5idase

converts :2?2 into :2? and nascent ? which o5idise the substrate into

coloured substrate. The intensity of colour will give the concentration of

glucose.. The above reagent mi5ture can also be mounted on a plastic 3lm. 8 drop of

blood is added. The intensity of dye is measured by glucometer.

METABOLISM IN T;E WELL * FE% STATE

!) The absorptive state is the 2 to hours period after ingestion of a normal meal./uring this period transient increase in plasma glucose, amino acid, and

triacylglycerols occur. slet tissue of the pancreas responds to the elevation level of

glucose and amino acids with an increased of insulin and a drop in the secretion of

glucagons. t is an anabolic period (increased synthesis of glycogen, triacylglycerols

and protein). /uring this absorptive period all tissues use glucose as fuel.

2) En=)mi& &han"es in the 'e! state: The Fow of intermediates through metabolic

pathways is controlled by four mechanisms#

a. The availability of substrates

b. 8llosteric activation and inhibition of en6ymes

c. Covalent modi3cation of en6ymes and

d. nduction repression of en6yme synthesis.

) Allosteri& e>e&ts: The allosteric changes usually a


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Thus, after a meal, the liver receives portal blood containing absorbed nutrients and

high levels of insulin secreted by the pancreas

8. 6aroh)!rate metaolism: :epatic metabolism of glucose is increased by the

following mechanism#

a. In&rease! +hos+hor)lation o' "lu&ose: :igh levels of intra cellular

glucose in the hepatocyte stimulates glucoinase to phosphorylate glucose to

glucose 4$phosphate .. In&rease! "I)&ol)sis: The conversion of glucose to pyruvate to acetyl Co8

is stimulated by the elevated insulin to glucagon ratio that activates the ey

en6ymes of glycolysis 8cetyl Co8 is used as either provides energy by

o5idation by the TC8 cycle or as a building bloc for fatty acid synthesis

&. In&rease! a&ti#it) o' the he2ose mono+hos+hate +ath3a)


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. Fat Metaolism

!. In&rease! s)nthesis o' 'att) a&i!s: /e novo synthesis of fatty acids from

acetyl Co8 in adipose tissue is nearly undetectable in humans, e5cept when

refeeding a previously fasted individual. >ost of the fatty acids added to the lipid

stores of adipocytes is provided by dietary fat (in the form of chylomicrons), and

a lesser amount is supplied by I1/1 from the liver

2. In&rease! tria&)l"l)&erol s)nthesis: 8dipocytes lac glycerol inase, so thatglycerol $phosphate used in triacylglycerol synthesis must come from the

metabolism of glucose Thus, in the well$fed state, elevated levels of glucose and

insulin favor storage of T

"atty acid K glycerol $ph triacylglycerol (T)

. %e&rease! tria&)l"l)&erol !e"ra!ation: nsulin inhibits the hormone$sensitive

lipase (dephosphorylated form) and thus inhibits triacylglycerol degradation is in

the well$fed state.

RESTING S7ELETAL M5S6LE:

!. 8t rest, muscle accounts for about 0J of the o5ygen consumption of the body during

vigorous e5ercise it is responsible for up to ;0J of the total o5ygen consumption. Beletal

muscle despite its potential for transient periods of anaerobic glycolysis is an o5idative

tissue.

2. :eart muscle di


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low to be an energy source. f the blood glucose levels fall below appro5imately 0 mg %dl

(normal blood glucose is 70$;0 mg%dl) cerebral function is impaired.

8. 6aroh)!rate Metaolism: n the well$fed state, the brain uses glucose e5clusively as a

fuel, completely o5idi6ing about !0 g % day glucose to carbon dio5ide and water. The

brain contains no stores of glycogen, and is therefore completely dependent on the

availability of blood glucose.

+. Fat Metaolism: The brain has no signi3cant stores of triacylglycerols. +lood fatty acidsdo not eEciently cross the blood$brain barrier (The endothelial cells that line the blood

vessels in the brain).Thus, the o5idation of fatty acids is of little importance to the brain

METABOLISM IN FASTING

8. "asting may result from an inability to obtain food, from the desire to lose weight

rapidly, or in clinical situations in which an individual cannot eat because of trauma,

surgery, neoplasmas and burns. n the absence of food, plasma levels of glucose,

amino acids, and triaclyglycerols fall, stimulating the secretion of glucagon and

inhibiting insulin secretion.

+. "asting is a catabolic period characteri6ed by degradation of glycogen, triaclyglycerols,

and protein to#

a. >aintain suEcient plasma levels of glucose for energy metabolism of the brain

and other glucose G reDuiring tissues

b. >obili6e fatty acids from adipose tissue and etone bodies from liver to supply

energy to all other tissues .

C. Fuel Stores: The metabolic fuels available in a normal 70$Lg man at the beginning of

a fast are# (!) != Lg fat, (2) 0.2 Lg glycogen, and 4 Lg protein. ?nly about !% of the

body protein can be used for energy production without a


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when the concentration of acetyl Co8, produced from fatty acid

o5idation e5ceeds the o5idative capacity of the tricarbo5ylic acid (TC8)

cycle. nlie fatty acids Letone bodies are water Gsoluble, and appear

in the blood and urine by the second day of a fast.

A. A!i+ose Tissue in Fastin":

a. 6aroh)!rate Metaolism: lucose transport into the adipocyte and its

metabolism are depressed due to low levels of blood insulin .This leads to adecrease in fatty acid and triacyl$ glycerol synthesis.

. Fat Metaolism:

i. In&rease! !e"ra!ation o' tria&l)"l)&erols# The activation of

hormone G sensitive lipase and subseDuent hydrolysis of stored

triacylglycerol are stimulated by high levels of catecoholamines

(epinephrine and particularly norepinephrine).

ii. In&rease! release o' 'att) a&i!s: "atty acids resulting from the

hydrolysis of stored triacylglycerol are released into the blood. +ound to

albumin, they are transported to other tissues for use as fuel. &art of the

fatty acids is o5idi6ed in the adipose tissue to produce energy. The

glycerol produced from triacylglycerol degradation is used by the liver

for gluconeogenesis.

iii. %e&rease! u+tae o' 'att) a&i!: n fasting, lipoprotein lipase activity

of adipose tissue is low. Thus, circulating triacylglycerol of lipoproteins is

not available for triacylglycerol synthesis in adipose tissue.

". Restin" Seletal Mus&le in Fastin":

a. *esting muscle uses fatty acids as its maor fuel source. +y contrast, e5ercising

muscle initially uses its glycogen stores as a source of energy. /uring intense

e5ercise, glucose $4$phosphate derived from glycogen is converted to lactate

by anaerobic glycolysis. 8s these glycogen reserves are depleted, free fatty

acids provided by the mobili6ation of triacylglycerol from adipose tissue

become the maor sources.

b. Carbohydrate >etabolism# lucose transport and subseDuent glucosemetabolism are depressed because of low blood insulin.

c. Fat Metaolism: /uring the 3rst 2 wees of fasting, muscle uses fatty acids

from adipose tissue and etone bodies from the liver as fuels. 8fter about

wees of fasting, muscle decreases its utili6ation of etone bodies and o5idi6e

only fatty acids. This leads to a further increase in the already elevated levesl

of blood etone bodies.

d. 9rotein Metaolism: /uring the 3rst few days of starvation there is rapid

breadown of muscle protein, giving amino acids that are used by the liver for

gluconeogenesis. 8lanine and glutamine are Duantitatively the most important

glucogenic amino acids released from muscle. 8fter several wees of fasting,

the rate of muscle proteolysis decreases due to a decline in the need for

glucose as a fuel for brain

. Brain in Fastin": /uring the 3rst days of fasting, the brain continues to use only

glucose as a fuel. n prolonged fasting ( greater than 2$ wees ) , plasma etone

bodies reach maredly high levels and are used in addition to glucose as a fuel by

the brain. This decreases the need for protein catabolism for gluconeogenesis.

%iaetes mellitus

Short notes:

1. inter+retation o' "lu&ose toleran&e test* O&t ,-


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. Gl)&oselate! haemo"loin* Au" //0. GTT C Dune 1,,/. 6on(rmator) tests 'or the !ia"nosis o' !iaeti& mellitus* A+ril 1,,-4. Glu&ose toleran&e test A+ril 1,,- A+ril 1,,,

ntroduction#

a. >etabolic disease due to absolute or relative de3ciency of insulin

b. ncidence is ! per !0 persons of total populationc. Criteria for diagnosis#d. fasting blood is more than !24 mg%dl on more than one occasione. one value of N200 mg%dl after glucose load

Classi3cation#

!. Type #a. = J of diabetic casesb. nsulin dependantc. insulin level is de3cient

i. immune mediatedii. idiopathic

d. onset below 0 years of age

e. more prone for etosisf. circulating antibodies against insulin are seen in =0J casesg. antibodies against islet cell cytoplasmic proteins are seen in -0J cases

2. Type #a. Hon insulin dependent (H//>)b. Circulating insulin level is normal, mildly elevated or slightly decreasedc. "urther classi3ed as#

i. ?beseii. Hon obeseiii. >aturity onset diabetes of young (>?/@) this is due to defective

lucoinase and increase in threshold for glucose induced insulin

secretiond. >ainly due to decreased biological response to insulin$ insulin resistance

e. sual age is above 0 yearsf. 1ess prone to develop etosisg. 40J are obese and may have increase insulin level

. /iabetic prone states#a. estationalb. mpaired glucose tolerancec. mpaired fasting glycaemia

. Becondary to other causes#a. Andocrine# Cushings disease thyroto5icosis acromegalyb. /rug induced# steroids beta blocersc. &ancreatic disease# chronic pancreatitis calculus pancreas hemochromatosis

cystic 3brosis=. >etabolic syndrome or insulin resistance syndrome of diabetes# this is characterised

by#a. 8bdominal obesityb. ncreased blood triglycerides and low :/1 cholesterolc. :igh +&d. /ue to insulin resistance or decreased glucose tolerancee. ncreased ris of coronary artery diseasef. >ore common in developing countriesg. Bome may have genetic predisposition for this syndromeh. &hysical inactivity is another important factori. Criteria for diagnosis#


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i. Oaist more than 0P in men =P in womenii. Triglyceride N !=0 mg%dliii. :/1 ' 0 in men and , =0 in women (mg%dl)iv. +& N !0%-=v. "asting glucose N!00 mg%dl

. >anagement#i. A5ercise

ii. Oeight reductioniii. 1ess fat, trans fatty acid and cholesterol in diet

4. >etabolic derangement in /iabetes mellitus#a. Carbohydrate metabolism#

i. /ecreased uptae of glucose by cellsii. nhibition of lycolysisiii. Btimulation of neoglucogenesisiv. :yperglycaemia

b. 1ipid metabolism#i. ncrease in free fatty acids and fatty liverii. nutilised acetyl Co8 is diverted to etone bodies leading to etosisiii. :yperlipidemia ( increase in HA"A,T8 and cholesterol)

c. &rotein metabolism#

i. ncrease in protein breadownii. >uscle wasting7. Clinical presentations#

i. lucosuriaii. &olyuriaiii. &olydipsiaiv. &olyphagiav. Oasting

vi. *ecurrent infections and tuberculosis due to glucose providing

nutrition for microbs and deranged macrophage activity-. Complications#

!. 8cute#i. Letoacidosis# more common in type more acetyl Co8 converted into

etones also metabolic acidosis acidotic breathing is called Lussmaulrespiration can lead to coma

ii. ncreased blood glucose causes hyperosmolality and lead to nonetotic

coma2. Chronic#

iii. 8therosclerosis and microangiopathyiv. Cataract and retinopathyv. &eripheral neuropathy

;. 1ab tests#!. +lood and urinary glucose monitoring2. 1ipid pro3le. rea and creatinin levels. >icroalbuminuria (=0$00 mg%day) and fran albuminuria

,. Glu&ose toleran&e test#. Btandardise test=. seful in doubtful cases4. Ho TT for con3rmed cases7. t is also diagnostic of renal glycosuria

&rocedure for TT#!. ood carbohydrate diet days prior to test2. 0$=0 gm of carbohydrate diet in the previous night. 8void drugs that alter glucose level and e5ercise and smoing. Btarvation from - &> previous night.=. 8t - am fasting blood and urine samples are collected


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4. lucose loading# 7= gm of glucose in 200 to 00 ml of water to drin in =

minutes.7. +lood and urine samples are collected at 9 hr intervals-. >ini TT# only fasting and 2 hour samples are collected.

*esults#

!. Hormal pattern# blood glucose level reaches a pea after ! hour and comes

down to fasting level in 2 9 hours none of urine sample will show presence of

glucose.2. /iabetes mellitus#

!. fasting blood is more than !24 mg%dl on more than one occasion2. one value of N200 mg%dl after glucose load

. mpaired tolerance# the values lie between normal and diabetic states. estational diabetes# carbohydrate intolerance for the 3rst time only

during pregnancy=. 8limentary glycosuria# within 2 hour samples are normal but a pea rise

after 2 hrs occurs due to increased alimentary absorption of glucose e.g.

astrectomy and hyperthyroidism4. *enal glycosuria# normal renal threshold is !7=$!-0 mg%dl if urine sugar is

positive when blood glucose is normal it is called renal glycosuria this is

due to impairment of tubular re absorption of glucose e.g. &regnancy,

"anconi syndrome7. n diabetic nephro sclerosis urine sugar may be absent even in high blood

glucose levels

"actors a


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Gl)&ate! ;:


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in three places before secretion to form the C$peptide and the active insulin

molecule containing the 8 and + chains.

2. nsulin is 3rst synthesi6ed as preproinsulin which is changed to insulin as follows#

&re pro insulin(!0; aminoacids) pro insulin (-4 aminoacids) insulin (=!

aminoacidsC peptide is removed)

.

. &reproinsulin and pro insulin are inactive. nsulin is stored in the cytosol in

granules that are released by e5ocytosis. nsulin is degraded by the en6yme

insulinase present in the liver and to a lesser e5tent in the idneys.

=. nsulin has a plasma half$life of about 4 minutes. This short duration of action

permits rapid changes in circulating levels of the hormone. Hormal insulin level is

=$!= micro units % ml of blood

4. nsulin and C$peptide are synthesi6ed and secreted in eDuimolar Duantities.

Therefore, measurement of C$peptide is an inde5 of rate of secretion of insulin.

7. >utations causing changes in amino acid seDuence at the cleavage points can

lead to familial pro$insulinemia.

Re"ulation o' Insulin Se&retionStimulation o' insulin se&retion:

!. The relative amounts of insulin and glucagon secreted by the pancreas are

regulated so that the rate of hepatic glucose production is ept eDual to the use

of glucose by peripheral tissues.

2. Glu&ose: ingestion of glucose or a carbohydrate rich meal leads to a rise in blood

glucose which stimulates insulin secretion. lucose is the most important

stimulus for insulin secretion. 8s blood glucose level increases, the insulin

secretion also correspondingly increases. lucose induces a biphasic response to

insulin secretion. 8 discharge of insulin from the beta cell storage pool occurs

during the initial rapid phase of insulin release within 3rst 2 minutes. The second

phase of insulin release lasting for =$!0 minutes is of smaller magnitude and is

due to discharge of newly synthesi6ed hormone. +eta cells have luT 2 receptors

for glucose absorption 8T& stimulates the receptor protein and calcium channel

is opened. ncreased intracellular Ca causes insulin secretion

. Amino A&i!s: ingestion of protein leads to a rise in plasma amino acids which

stimulate insulin secretion. Alevated plasma arginine is a particularly potent

stimulus for insulin secretion

. Gastrointestinal hormones: The intestinal peptide secretin as well as other

gastrointestinal hormones, stimulate insulin secretion after the ingestion of the


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food. They cause an anticipatory rise in insulin secretion. The same amount of

glucose given orally stimulates more insulin secretion than if given intravenously.

Inhiition o' insulin se&retion:

!. The synthesis and release of insulin are decreased during starvation and stress.

These e


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a. ptae of lucose by Tissues# nsulin facilitates the membrane transport

of glucose. "acilitated di&

shunt pathway2. nhibition of lipolysis# nsulin inhibits lipolysis through inhibition of

hormone sensitive lipase. 8nti$etogenic A Co8 synthase and so etogenesis is

decreased.2. n presence of insulin, acetyl Co8 is completely utili6ed in the citric

acid cycle. &roduction of etone bodies reduced

=. 9rotein metaolism#!. "avour protein synthesis reduces protein degradation2. :as anabolic e


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peptide is essential for proper insulin folding. The number of amino acids in C

peptide may vary according to species. nsulin with =! amino acids is thus

formed. ADuimolar amounts of C$peptide and insulin are then stored in secretory

granules of the pancreatic beta cells and both are eventually released to the

portal circulation=. >easuring C$peptide can help to determine how much of own natural insulin a

person is producing as C$peptide is secreted in eDuimolar amounts to insulin.4. C$peptide levels are measured instead of insulin levels because C$peptide

can assess a personMs own insulin secretion even if they receive insulin

inections, and because the liver metaboli6es a large and variable amount of

insulin secreted into the portal vein but does not metabolise C$peptide,

meaning blood C$peptide may be a better measure of portal insulin secretion

than insulin itself.7. 8 very low C$peptide con3rms Type ! diabetes and insulin dependence and is

associated with high glucose variability, hypoglycaemia and increased

complications.-. C$peptide may be used for determining the possibility of gastrinomas

associated with >ultiple Andocrine Heoplasm syndromes (>AH !).;. C$peptide levels may be checed in women with &olycystic ?varian Byndrome

(&C?B) to help determine degree of insulin resistance.!0. Therapeutics# *ecent studies suggests that Beveral physiological ee&ts o' Glu&a"on:

1. A


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4. Me&hanism o' a&tion o' "lu&a"on :

1. lucagon binds to high$aEnity receptors on the cell membrane of the

hepatocyte S activation of adenylate cyclase in the plasma membraneS

increase c8>& (second messenger).

. c8>& activates protein inase and increases the phosphorylation of speci3c

en6ymes or other proteins. The phosphorylation activates or inhibits the ey

regulatory en6ymes of carbohydrate and lipid metabolism.;9OGL6EMIA

!. :ypoglycemia is characteri6ed by#

a. Central nervous system symptoms, including confusion, aberrant behavior, or

coma

b. 8 simultaneous blood glucose level eDual to or less than 0 mg%dl and

c. Bymptoms being corrected within minutes following the administration of

glucose. :ypoglycemia is a medical emergency

2. The central nervous system has an absolute need for a continuous supply of blood

glucose as a fuel for energy metabolism. Transient hypoglycemia can causes

cerebral dysfunction, but severe, prolonged hypoglycemia causes brain death. The

most important hormonal changes to correct hypoglycemia are elevated glucagon

and epinephrine combined with decrease insulin secretion.

. S)m+toms o' h)+o"l)&emia: The symptoms of hypoglycemia can be divided to

two groups,

a. A!rener"i& s)m+toms: 8n5iety, palpitation, tremor, and sweat. These

symptoms are due to increased epinephrine secretion regulated by the

hypothalamus due to hypoglycemia. These symptoms occur when the blood

glucose levels fall rapidly.

b. Heuroglypenic Bymptoms# The decrease glucose supply to the brain leads to

brain dysfunction causing headache, confusion, slurred speech, sei6ures,

coma and death. These symptoms result from a gradual decrease in blood

glucose.. Glu&ore"ulator) S)stems: :umans have two overlapping glucose$regulating

systems that are activated by hypoglycemia#

a. The islets of 1angerhans, which secrete glucagon

b. The glucoreceptors in the hypothalamus stimulate the secretion of both

epinephrine (through the autonomic nervous system) and 8CT: and growth

hormone (:) by the anterior pituitary gland. lucagon, epinephrine, cortisol

and : are called the counterregulatory hormones because they antagoni6e

the action of insulin on glucose utili6ation.

c. Glu&a"on an! E+ine+hrine: :ypoglycemia is corrected by decreased

secretion of insulin and increased secretion of glucagon, epinephrine, cortisol,

and growth hormone. lucagon and epinephrine are most important in the

acute, short$ term regulation of blood glucose levels. lucagon stimulates

hepatic glycogenolysis and gluconeogenesis. Apinephrine stimulates

glycogenolysis and lipolysis, inhibits insulin secretion, and inhibits insulin

dependent uptae of glucose by tissues.

d. 6ortisol an! Gro3th hormone: These hormones are less important in the

short term regulation of blood glucose levels, but they are important in the

long term regulation of glucose metabolism. They stimulate gluconeogenesis.

=. T)+es o' h)+o"l)&emia: :ypoglycemia may be divided into three groups


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a. Insulin in!u&e! h)+o"l)&emia: :ypoglycemia occurs freDuently in patients

with diabetes receiving insulin treatment. >ild hypoglycemia in fully

conscious patients is treated by oral administration of carbohydrate. >ore

commonly, patients with hypoglycemia are unconscious or have lost the

ability to coordinate swallowing. n these cases, glucagon, administered

subcutaneously or intramuscularly, is the treatment of choice

b. 9ost+ran!ial h)+o"l)&emia: This is the second most common of the formof hypoglycemia t is caused by an e5aggerated insulin release following a

meal, causing a transient hypoglycemia with mild adrenergic symptoms. The

blood glucose level returns to normal even if the patient is not fed. The only

treatment usually needed is that the patient eat freDuent small meals instead

of the usual three large meals.

c. Fastin" h)+o"l)&emia: t is rare and produces neuroglycopenic symptoms.

t may be due to#

a) *eduction in the rate of glucose production by the liver as in patients

with hepatocellular damage or adrenal insuEciency or in fasting

persons who have consumed large Duantities of ethanol which inhibits

gluconeogenesis. 8lcohol consumption can also increase the ris for

hypoglycemia in patients using insulin

b) 8n increased rate of glucose utili6ation by the peripheral tissues, most

commonly due to elevated insulin resulting from a pancreatic b$cell

tumor. f untreated, a patient with fasting hypoglycemia may lose

consciousness and develop convulsions and coma.

Documents

11. Integration of Metabolism New Version 2