DIABETES MELLITUS

It is a syndrome of impaired carbohydrate, protein and fat metabolism caused by either lack of insulin secretion or decreased sensitivity of tissues to insulin.

TYPES Type 1 diabetes mellitus or insulin dependant diabetes mellitus. Type 2 diabetes mellitus or non insulin dependant diabetes mellitus.

α- and β-cells in the islets of Langerhans of the pancreas

ENDOCRINE CELLS ALPHA or A Cells BETA or B Cells DELTA or D Cells F Cells

Factors Affecting Insulin Secretion Stimulators Inhibitors Glucose Somatostatin Mannose 2-Deoxyglucose Intestinal hormones [GIP, GLP-1 (7-36), gastrin, secretin, CCK; others?] α-Adrenergic stimulators [nor-epinephrine, epinephrine] β-Keto acids Acetylcholine β-Adrenergic blockers [propranolol] Cyclic AMP and various cAMP-generating substances Diazoxide Thiazide diuretics β-Adrenergic stimulators K+ depletion Theophylline Phenytoin Sulfonylureas Alloxan

Fasting [mg/dl] Blood Glucose 2 hrs after B/F [mg/dl] Blood Glucose Normal < 100 < 120 Borderline < 130 < 150 Diabetic > 130 > 150

ACTIONS OF INSULIN CHO Metabolism Fat Metabolism Protein Metabolism Cell Growth

Principal Actions of Insulin Rapid [seconds] Increased transport of glucose, amino acids, and K+ into insulin-sensitive cells

Principal Actions of Insulin Intermediate [minutes] Stimulation of protein synthesis Inhibition of protein degradation Activation of glycolytic enzymes and glycogen synthase Inhibition of phosphorylase and gluconeogenic enzymes

Principal Actions of Insulin Delayed [hours] Increase in mRNAs for lipogenic and other enzymes

ADIPOKINES Agent Effect on Insulin Resistance Leptin Decreases TNFα Increases Adiponectin Resistin

Plasma Glucose Levels at Which Various Effects of Hypoglycemia Appear

Regulation of secretion of glucagon and insulin

Factors Affecting Glucagon Secretion Stimulators Inhibitors Amino acids [particularly the glucogenic amino acids: alanine, serine, glycine, cysteine, and threonine] Glucose CCK, gastrin Somatostatin Cortisol Secretin Exercise FFA Infections Ketones Other stresses Insulin β-Adrenergic stimulators Phenytoin Theophylline α-Adrenergic stimulators Acetylcholine GABA

PHYSIOLOGY OF DIAGNOSIS Urinary glucose Fasting blood glucose and insulin levels Glucose tolerance test Acetone breath

TREATMENT OF DIABETES Dieting Exercise Weight loss Drugs to cause increased insulin sensitivity Drugs to cause increased insulin secretion Administration of insulin