New Concepts in Diabetes and Its Treatment - part 1 ppt

[...]... Diabetes mellitus Diabetes Care 19 97;20 :11 83 11 97 Fajans SS: Classification and diagnosis of diabetes; in Rifkin H, Porte D (eds): Diabetes mellitus Theory and Practice, ed 4 New York, Elsevier, 19 90, pp 346–356 International Diabetes Federation (IDF), 19 98 19 99 European Diabetes Police Group: A Desktop Guide to Type 2 (Non-Insulin-Dependent) Diabetes mellitus Brussels, IDF, 19 99 National Diabetes Data... Ospedale Garibaldi, Catania, Italy Insulin Secretion Introduction Pancreatic -cells synthesize a large polypeptide chain, the proinsulin, which is then cleaved into the so-called connecting peptide (C-peptide) and the insulin molecule, composed of two peptide chains containing 51 amino acid residues Both insulin and C-peptide are packaged in the secretory granules During the secretory process, the granule... 2-Adrenergic receptor; AC>adenylate cyclase; cAMP>cyclic AMP; DAG >1, 2-diacylglycerol; GK>glucokinase; Glg>glucagon receptor; GLP1>glucagon-like peptide 1; Gq>a further type of G protein; Gs and Gi>stimulatory and inhibitory G proteins; IP3>inositol -1 , 4,5-trisphosphate; M3>a type of muscarinic receptor; PIP2>phosphatidylinositol-4,5-P; PKA>protein kinase A; PKC>protein kinase C; PLC>phospholipase C Insulin... glucose in ow to the circulation by in uencing the rate of gastric emptying and would also inhibit hepatic glucose production in the postprandial period Assessment of Insulin Secretion Fasting Insulin Level The fasting insulin level (normally between 5 and 15 U/ml) may reflect the insulin secretory capacity It may be very low (=5 U/ml) in subjects with high insulin sensitivity (lean and/ or trained subjects)... glycemia in the portal vein increases (such as during the absorption Insulin Secretion and Its Pharmacological Stimulation 21 period), whereas its presence in the -cells allows these cells to perceive the increase in blood glucose and to respond with adequate insulin release In order to stimulate insulin release, glucose must first be transported into the -cell by the glucose transporter (GLUT-2 isoform), and. .. develop diabetes within 15 Belfiore/Iannello 12 Table 1 Etiologic classification of diabetes mellitus 1 Type 1 diabetes A Immune-mediated B Idiopathic 2 Type 2 diabetes 3 Other specific types A Genetic defects of -cell function (MODY -1 , MODY-2, MODY-3, mitochondrial DNA, and others) B Genetic defects in insulin action (type A insulin resistance, leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetes, ... are also called incretins They include: the gastric inhibitory polypeptide (GIP), secreted by the endocrine cells of duodenum and jejunum; cholecystokinin (CCK), both the long (CCK-33) and the short (CCK-8) peptide chain, released by duodenum and proximal part of jejunum after ingestion of fats and proteins; the glucagon-like peptide -1 (7–36) amide, or GLP -1 (7–36), formed from GLP -1 (the precursor... discharged outside the -cell through a process of exocytosis, leading to the release of insulin and C-peptide in equimolar amounts, together with small quantities of uncleaved proinsulin In contrast to insulin, C-peptide is not taken up by the liver (and the other insulin-sensitive tissues), and therefore its plasma level is a good index of insulin secretion Regulation of Insulin Secretion by Substrates... and lipid metabolism Specifically, glucose metabolism leads to the generation of malonyl-CoA, which inhibits carnitine palmitoyltransferase -1 , with the attendant accumulation of long-chain acyl-CoA esters in the cytosol (see also chapter III and figure 3) Malonyl-CoA and long chain acyl-CoA esters may act as metabolic coupling factors in -cell signalling Belfiore/Iannello 22 Fig 1 Regulation of insulin... Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance Diabetes 19 79;28 :10 39 10 57 O’Sullivan JB: Diabetes mellitus after GDM Diabetes 19 93;40(suppl) :13 1 13 5 Velho G, Blanche H, Vaxillaire M, et al: Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families Diabetologia 19 97;40: 217 –224 World Health Organization: Diabetes . cases of diabetes mellitus falls into two major forms: type 1 and type 2 diabetes. Type 1 Diabetes Immune-Mediated Type 1 Diabetes Type 1 diabetes (previously also named insulin-dependent diabetes. Chichester, Wiley, 19 99. Belfiore F (ed): Frontiers in Diabetes. Basel, Karger, vol 8 /19 87, vol 9 /19 90, vol 10 /19 90, vol 11 /19 92, vol 12 /19 93, vol 14 /19 98. Bray G, Bouchard C, James WPT (eds): Handbook of. (eds): New Concepts in Diabetes and Its Treatment. Basel, Karger, 2000, pp 1 2 Introduction Diabetes mellitus and its complications are clinical conditions of growing importance both from the clinical