Lecture 17-Diabetes

Problems with control of glucose metabolism

• Normal Glucose is 90 mg/dl or 0.9 g/l. For an individual with 4 liter blood volume, normal levels are 3.6 gm.

• Below 45 mg/dl may result in hypoglycemic shock (coma)

• Persistent level above 125 mg/dl indicates diabetes-results in renal, vascular, eye disease and periodontitis

Hyperglycemia Can Cause Serious Long-Term Problems

Periodontal disease

• Glucose stimulates the secretion of insulin and suppresses the secretion of glucagon.

• Insulin is synthesized in RER of beta cells and is packaged in to secretary vesicles in the golgi.

• Insulin secretion is initiated by increased ATP/ADP ratio within the cell.

• This condition closes membrane ATP sensitive K channel and depolarizes the cell.

• The voltage change opens up another channel-the Ca channel. The entry of Ca into the cell stimulated the first short phase.

• The second prolonged phase requires other signaling like the increased concentration of cytosolic long chain fatty acyl CoA molecules. Diacyl glycerol and protein kinase C signaling.

Age related onset of type 2 diabetes

Glucose tolerance test for diabetes

ABC’s

A – A1c, or hemoglobin A1c test. ADA goal is 7% or less.

AACE goal is 6.5% or less.

B – Blood pressure < 130/80 mmHg for non-pregnant adults.

C – Cholesterol HDL (good) cholesterol – >40 mg/dl (men); >50 mg/dl

(women)

LDL (bad) cholesterol – <100 mg/dl

Triglycerides – <150 mg/dl

Classification of Diabetes

Type I Autoimmune destruction of β-cells

Type II Insulin resistance and β-cell failure

Other types Genetic defects (mutations of glucokinase gene; insulin resistance; antireceptor antibodies;Drugs and chemically induced; Down’s syndrome

Gestational Diabetes

Glucose intolerance-Diabetes diagnosed in pregnancy

Type I and Type II

Type I Type II

Onset Under 20 yr Usually over 40 yr

Insulin synthesis

Absent Impaired beta-cell function and insulin resistance

Plasma insulin

Low or absent Low, normal or high

Islet cell antibodies

Yes No

Obesity Uncommon Common

Keto acidosis

Yes Possible

Non-enzymatic protein modification by excess glucose

Ketone body formation

• Diabetes and Starvation• Excessive Fatty acid oxidation in mitochondria

Acetyl CoA + Acetyl CoA

Acetoacetyl-CoA

Β-Hydroxy-β-methyl Glutaryl-CoA(HMG-CoA)

Acetoacetate

Acetone + CO2 D-β-hydroxybutyrate

NADH + H+

Plasma concentration of Ketone Bodies in starvation

Ketone Bodies utilization

• Can be used by heart, brain and muscle for energy

D-β-hydroxybutyrate

Acetoacetate

Acetoacetyl CoA

Acetyl CoA + Acetyl CoA

Succinyl CoA

Succinate

Succinyl CoA:Acetoacetate

CoA Transferase

CoAThiolase

Red and swollen gums thatbleed, often during brushingor flossing

Gums that have pulled awayfrom the teeth, leaving moreof the crown of the toothexposed and eventuallysome amount of the toothroot.

Milky white or yellowishplaque deposits, which areusually heaviest betweenteeth.

Symptoms of Periodontal disease

1. Offensive and foul odor from the oral cavity

2. Burning sensation in the mouth or the tongue

3. Dry mouth-sores, infection, ulcers and tooth decay

4. Delayed wound healing

Learning Objectives lecture 17

1. What are plasma glucose concentrations in physiologically normal, pre-diabetic and diabetic individuals?

2. What is the mechanism of insulin release from the beta cells?

3. How is this release affected in type I and type II diabetics?

4. How does metabolism change in diabetic individuals?

5. How does high concentration of plasma glucose modify membrane function?

6. What is a glucose tolerance test and how it interpreted?

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