1. 15.10.2003inse.ppt1 Glucose homeostasis Insulin lowers blood glucose (yes, but...) Insulin enables glucose metabolism in cells (yes, but...) Insulin exerts its effect through insulin receptor a transmembrane protein with kinase activity Key point of postreceptor events (a complicated cascade) is the translocation of glucose transporter GLUT4 to the membrane of muscle and fat cells THE PLAYERS OF THE GAME : GLUCOSE, INSULIN INSULIN RECEPTOR GLUCOSE TRANSPORTER

2. 15.10.2003inse.ppt2 GLUT4 IR glucose

3. 15.10.2003inse.ppt3 GLUT4 IR INSULIN glucose

4. 15.10.2003inse.ppt4 GLUT4 IR INSULIN glucose

5. 15.10.2003inse.ppt5 Insulin effects synthesis of glycogen glycolysis synthesis of fatty acids and their esterification synthesis of proteins glycogenolysis and gluconeogenesis oxidation of fatty acids and lipolysis INSULIN IS ANABOLIC HORMONE

6. 15.10.2003inse.ppt6 GLUT4 IR INSULIN glucose

7. 15.10.2003inse.ppt7 „disorder of secretion and disturbance of function“ performance of B cells burden - obesity

8. 15.10.2003inse.ppt8 Secretion disorder is the first Genes regulating the intrauterine development of Langerhans islets Lessons from an extreme rare condition transient neonatal diabetes Small babies and DM2

9. 15.10.2003inse.ppt9 Different performance Different burden

10. 15.10.2003inse.ppt10 Allostasis instead of homeostasis (no free lunch)

11. 15.10.2003inse.ppt11 TYPE 2 DIABETES IN THE WORLD  1994 - REALITY  WORLD 99 million / 1.8 %  EUROPE 16 million / 3.1 %  2010 - FORECAST 216 million / 3.8 % 24 million / 4.8 % MORE FOOD & WESTERNIZATION  OBESITY AGING OF POPULATION IN MOST COUNTRIES UNDIAGNOSED DIABETES MELLITUS!

12. 15.10.2003inse.ppt12 TYPE 2 DIABETES IS THE TIP OF THE ICEBERG 4 % TYPE 2 DIABETES MELLITUS often undiagnosed usual diagnosed too late  microvascular complications present atherosclerosis accelerated 12 % IMPAIRED GLUCOSE TOLERANCE* atherosclerosis accelerated cca 25 % INSULIN HYPERSECRETION (INSULIN RESISTANCE, X-SYNDROME) impaired sympathetic regulation ? obesity, hypertension, impaired lipid status atherosclerosis accelerated

13. 15.10.2003inse.ppt13 CVD & DM 2 PREVENTION, 2000   NUTRITION  energy  composition, micronutrients   SMOKING & ALCOHOL   HUNTING & GATHERING  (PHYSICAL ACTIVITY)  HEALTH AWARENESS   weight control  blood lipids, glucose  blood pressure  inherited and acquired health risks 55% S, 30% F, 15% P