New Concepts in the Pathogenesis of NIDDM (Advances in Experimental Medicine and Biology, 334)

The pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) has attracted the interest of our group during the last three decades. As early as 1969, a Nobel Symposium dealing with this topic was organized in Stockholm. This was followed in 1987 by a Nobel Conference devoted to the same subject. The main purpose of these meetings was to bring together the most distinguished scientists from all over the world and present theories on molecular and genetic mechanisms responsible for the development of glucose intolerance in NIDDM. This idea was followed also in the present symposium, "New Concepts in the Pathogenesis of NIDDM," organized with diabetologists from Toronto in Canada. Our purpose is to biannually organize international meetings covering important aspects of dia­ betes research, hoping that this type of interaction may result in new concepts and treat­ ment alternatives. For us, participating in this symposium in September 1992, the meeting in Stockholm was very stimulating and innovative. It is a special pleasure that almost all invited lecturers submitted manuscripts. Thus, the publication of the proceedings of the symposium makes it possible for all interested in diabetes research to share new ideas and findings presented at the meeting. Claes-G6ran Ostenson Suad Efendic Mladen V ranic v CONTENTS REGULATION OF INSULIN SECRETION Impaired Glucose-Induced Insulin Secretion: Studies in Animal Models with Spontaneous NIDDM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C. -G. Ostenson, A. Khan, and S. Efendic Perturbation ofIslet Metabolism and Insulin Release in NIDDM. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 WJ. Malaisse 2 Regulation of Cytoplasmic Free Ca+ in Insulin-Secreting Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Front Matter....Pages i-ix Impaired Glucose-Induced Insulin Secretion: Studies in Animal Models with Spontaneous NIDDM....Pages 1-11 Perturbation of Islet Metabolism and Insulin Release in NIDDM....Pages 13-23 Regulation of Cytoplasmic Free Ca 2+ in Insulin-Secreting Cells....Pages 25-45 The ß-Cell Sulfonylurea Receptor....Pages 47-61 Regulation of Glucose Transporters and the Na/K-ATPase by Insulin in Skeletal Muscle....Pages 63-78 Insulin Receptor: Aspects of its Structure and Function....Pages 79-88 The Diabetogenes Concept of NIDDM....Pages 89-100 Molecular Genetics of NIDDM and the Genes for Insulin and Insulin Receptor....Pages 101-111 Autoregulation of Glucose Transport: Effects of Glucose on Glucose Transporter Expression and Cellular Location in Muscle....Pages 113-127 Insulin Resistance and the Pathogenesis of Non-Insulin Dependent Diabetes Mellitus: Cellular and Molecular Mechanisms....Pages 129-150 Indirect Effects of Insulin in Regulating Glucose Fluxes....Pages 151-168 The Insulin-Antagonistic Effect of the Counterregulatory Hormones — Clinical and Mechanistic Aspects....Pages 169-180 On Insulin Action in Vivo: The Single Gateway Hypothesis....Pages 181-198 Acute Hormonal Regulation of Gluconeogenesis in the Conscious Dog....Pages 199-208 Estimating Gluconeogenic Rates in NIDDM....Pages 209-220 Glucose Metabolism During Physical Exercise in Patients with Noninsulin-Dependent (Type II) Diabetes....Pages 221-233 Substrates and the Regulation of Hepatic Glycogen Metabolism....Pages 235-252 Gluconeogenesis in Type 2 Diabetes....Pages 253-258 Regulation of Adipose Tissue Lipolysis, Importance for the Metabolic Syndrome....Pages 259-267 Cellular and Molecular Factors in Adipose Tissue Growth and Obesity....Pages 269-277 Regional Obesity and NIDDM....Pages 279-285 Hyperinsulinemia and VLDL Kinetics....Pages 287-294 Hyperinsulinism and Dyslipidemias as Coronary Heart Disease Risk Factors in NIDDM....Pages 295-301 A Paradigm to Link Clinical Research to Clinical Practice: The Challenge in Non-Insulin Dependent Diabetes Mellitus....Pages 303-310 Back Matter....Pages 311-316 The pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) has attracted the interest of our group during the last three decades. As early as 1969, a Nobel Symposium dealing with this topic was organized in Stockholm. This was followed in 1987 by a Nobel Conference devoted to the same subject. The main purpose of these meetings was to bring together the most distinguished scientists from all over the world and present theories on molecular and genetic mechanisms responsible for the development of glucose intolerance in NIDDM. This idea was followed also in the present symposium, "New Concepts in the Pathogenesis of NIDDM," organized with diabetologists from Toronto in Canada. Our purpose is to biannually organize international meetings covering important aspects of diaƯ betes research, hoping that this type of interaction may result in new concepts and treatƯ ment alternatives. For us, participating in this symposium in September 1992, the meeting in Stockholm was very stimulating and innovative. It is a special pleasure that almost all invited lecturers submitted manuscripts. Thus, the publication of the proceedings of the symposium makes it possible for all interested in diabetes research to share new ideas and findings presented at the meeting. Claes-G6ran Ostenson Suad Efendic Mladen V ranic v CONTENTS REGULATION OF INSULIN SECRETION Impaired Glucose-Induced Insulin Secretion: Studies in Animal Models with Spontaneous NIDDM ... ... ... ... ... ... ... C.-G. Ostenson, A. Khan, and S. Efendic Perturbation ofIslet Metabolism and Insulin Release in NIDDM. ... ... ... 13 WJ. Malaisse 2 Regulation of Cytoplasmic Free Ca+ in Insulin-Secreting Cells. ... ... ..