Glucose homeostasis Insulin lowers blood glucose yes but

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 GLUT 4 to the membrane of muscle and fat cells THE PLAYERS OF THE GAME: GLUCOSE, INSULIN RECEPTOR GLUCOSE TRANSPORTER 15. 10. 2003 inse. ppt 1

glucose IR GLUT 4 15. 10. 2003 inse. ppt 2

INSULIN glucose IR GLUT 4 15. 10. 2003 inse. ppt 3

INSULIN glucose IR GLUT 4 15. 10. 2003 inse. ppt 4

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 15. 10. 2003 inse. ppt 5

INSULIN glucose IR GLUT 4 15. 10. 2003 inse. ppt 6

„disorder of secretion and disturbance of function“ performance of B cells burden - obesity 15. 10. 2003 inse. ppt 7

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 DM 2 15. 10. 2003 inse. ppt 8

Different burden Different performance 15. 10. 2003 inse. ppt 9

Allostasis instead of homeostasis (no free lunch) 15. 10. 2003 inse. ppt 10

TYPE 2 DIABETES IN THE WORLD q 1994 - REALITY q WORLD q 2010 - FORECAST 216 million / 3. 8 % 99 million / 1. 8 % q EUROPE 24 million / 4. 8 % 16 million / 3. 1 % UNDIAGNOSED DIABETES MELLITUS! MORE FOOD & WESTERNIZATION Þ OBESITY AGING OF POPULATION IN MOST COUNTRIES 15. 10. 2003 inse. ppt 11

TYPE 2 DIABETES IS THE TIP OF THE ICEBERG 4 % TYPE 2 DIABETES MELLITUS often undiagnosed usual diagnosed too late Þ 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 15. 10. 2003 inse. ppt 12

CVD & DM 2 PREVENTION, 2000 Þ v NUTRITION Ø energy ß composition , micronutrients Ý v SMOKING & ALCOHOL ß v HUNTING & GATHERING Ý (PHYSICAL ACTIVITY) v HEALTH AWARENESS Ý Ø weight control Ø Ø Ø blood lipids, glucose blood pressure inherited and acquired health risks 15. 10. 2003 inse. ppt 55% S, 30% F, 15% P 13