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 IAutoimmune destruction of β-cells Type IIInsulin resistance and β-cell failure Other typesGenetic 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 IType II OnsetUnder 20 yrUsually over 40 yr Insulin synthesis AbsentImpaired beta-cell function and insulin resistance Plasma insulin Low or absentLow, normal or high Islet cell antibodies YesNo ObesityUncommonCommon Keto acidosis YesPossible

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 that bleed, often during brushing or flossing 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. Milky white or yellowish plaque deposits, which are usually heaviest between teeth. 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? 20