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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)

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Lecture 17-Diabetes

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  1. 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 Lecture 17-Diabetes

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

  3. Insulin Secretion by the -CellRoles of Glucose, K+, and Ca2+ Kir 6.2 Glucose entry Insulin secretion GLUT2 glucosetransporter Insulin secretory granules Glucokinase Ca2+ Glucose metabolism Ca2+ Ca2+ Ca2+ K+ ADP/ATP Ca2+ K+ K+ Calcium channel ADP/ATP SUR 1 K+ Potassium (KATP) channel KATP channel subunits: SUR 1=regulatory subunit; Kir 6.2=inward rectifying channel

  4. 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.

  5. Insulin Action in Muscle and Fat CellsMobilization of GLUT4 to the Cell Surface Plasma membrane Insulin receptor Intracellular signaling cascades Intracellular GLUT4 vesicles Insulin GLUT4 vesicle mobilization to plasma membrane GLUT4 vesicle integration into plasma membrane Glucose entry into cell via GLUT4 GLUT4=glucose transporter 4

  6. Age related onset of type 2 diabetes

  7. Glucose tolerance test for diabetes

  8. 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

  9. Non-enzymatic protein modification by excess glucose

  10. Classification of Diabetes

  11. Type I and Type II

  12. 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 Ketone body formation NADH + H+

  13. Plasma concentration of Ketone Bodies in starvation

  14. Can be used by heart, brain and muscle for energy D-β-hydroxybutyrate Acetoacetate Acetoacetyl CoA Acetyl CoA + Acetyl CoA Ketone Bodies utilization Succinyl CoA Succinate Succinyl CoA:Acetoacetate CoA Transferase Thiolase CoA

  15. 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 • Offensive and foul odor from the oral cavity • Burning sensation in the mouth or the tongue • Dry mouth-sores, infection, ulcers and tooth decay • Delayed wound healing

  16. Learning Objectives lecture 17 What are plasma glucose concentrations in physiologically normal, pre-diabetic and diabetic individuals? What is the mechanism of insulin release from the beta cells? How is this release affected in type I and type II diabetics? How does metabolism change in diabetic individuals? How does high concentration of plasma glucose modify membrane function? What is a glucose tolerance test and how it interpreted?

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