Lecture 17-Diabetes

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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

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Hyperglycemia Can Cause Serious Long-Term Problems
Periodontal disease
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• 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.

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Age related onset of type 2 diabetes
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Glucose tolerance test for diabetes
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ABCs

• A A1c, or hemoglobin A1c test.
• ADA goal is 7 or less.
• AACE goal is 6.5 or less.
• B Blood pressure
• lt 130/80 mmHg for non-pregnant adults.
• C Cholesterol
• HDL (good) cholesterol gt40 mg/dl (men) gt50
  mg/dl (women)
• LDL (bad) cholesterol lt100 mg/dl
• Triglycerides lt150 mg/dl

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Classification of Diabetes
Type I Autoimmune destruction of ß-cells
Type II Insulin resistance and ß-cell failure
Other types Genetic defects (mutations of glucokinase gene insulin resistance antireceptor antibodiesDrugs and chemically induced Downs syndrome
Gestational Diabetes Glucose intolerance-Diabetes diagnosed in pregnancy
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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
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Non-enzymatic protein modification by excess
glucose
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Ketone body formation

• Diabetes and Starvation
• Excessive Fatty acid oxidation in mitochondria
• Acetyl CoA Acetyl CoA
• Acetoacetyl-CoA
• ?-Hydroxy-ß-methyl Glutaryl-CoA
• (HMG-CoA)
• Acetoacetate
• Acetone CO2 D-ß-hydroxybutyrate

NADH H
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Plasma concentration of Ketone Bodies in
starvation
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Ketone Bodies utilization

• Can be used by heart, brain and muscle for energy
• D-ß-hydroxybutyrate
• Acetoacetate
• Acetoacetyl CoA
• Acetyl CoA Acetyl CoA

Succinyl CoA Succinate
Succinyl CoAAcetoacetate
CoA Transferase
CoA
Thiolase
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Symptoms of Periodontal disease
Milky white or yellowish plaque deposits, which
are usually heaviest between teeth.
Gums that have pulled away from the teeth,
leaving more of the crown of the tooth exposed
and eventually some amount of the tooth root.
Red and swollen gums that bleed, often during
brushing or flossing

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

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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?