Pathogenesis of Type 2 Diabetes Mellitus 6 - Chapter 6 : Diabetes...

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Contents Contributors Search TABLE OF CONTENTS NORMAL GLUCOSE HOMEOSTASIS SITE OF INSULIN RESISTANCE IN TYPE 2 DIABETES Hepatic Glucose Production Peripheral (Muscle) Glucose Uptake Splanchnic (Hepatic) Glucose Uptake Summary: Whole Body Glucose Utilization Glucose Disposal During OGTT Summary of Insulin Resistance in Type 2 Diabetes DYNAMIC INTERACTION BETWEEN INSULIN SENSITIVITY AND INSULIN SECRETION IN TYPE 2 DIABETES ROLE OF THE ADIPOCYTE IN THE PATHOGENESIS OF TYPE 2 DIABETES MELLITUS: THE DISHARMONIOUS QUARTET FFA and Muscle Glucose Metabolism Randle Cycle Revisited: Biochemical/Molecular Basis Of FFA-Induced Insulin Resistance FFA and Blood Flow FFA and Hepatic Glucose Metabolism Summary: FFA and the

Chapter 6 Pathogenesis of Type 2 Diabetes Mellitus 6

Eugenio Cersosimo, MD PhD - Associate Professor of Medicine, Department of Medicine, Division of Diabetes, UTHSCSA, Mail Code 7886 - 7703 Floyd Curl Drive, San Antonio, TX 78229-3900 Lawrence J Mandarino, PhD - Professor of the School of Life Sciences at Arizona State University and Professor of Medicine at the Mayo Clinic Arizona, Arizona State University, Center for Metabolic Biology, School of Life Sciences, Arizona State University , Tempe, AZ 85287-3704 Ralph A DeFronzo, MD - Professor of Medicine and ,Chair, Division of Diabetes , Department of Medicine, UTHSCSA, Mail Code 7886 - 7703 Floyd Curl Drive, San Antonio, TX 78229-3900 Updated December 15, 2011 TO OBTAIN A COMPLETE DOWNLOAD OF THIS CHAPTER IN PDF FORMAT, CLICK HERE

NORMAL GLUCOSE HOMEOSTASIS

In the postabsorptive state (10-12 hour overnight fast), the majority of total body glucose disposal takes place in insulin independent tissues (1). Under basal conditions approximately 50% of all glucose utilization occurs in the brain, which is insulin independent and becomes saturated at a plasma glucose concentration of about 40 mg/dl (2). Another 25% of glucose uptake occurs in the splanchnic area (liver plus gastrointestinal tissues) and also is insulin independent (3). The remaining 25% of glucose metabolism in the postabsorptive state takes place in insulin-dependent tissues, primarily muscle (4,5). Basal glucose utilization averages ~2.0 mg/kg.min and is precisely matched by the rate of endogenous glucose production (1,3-7). Approximately 85% of endogenous glucose production is derived from the liver, and the remaining amount is produced by the kidney (1,8,9). Approximately half of basal hepatic glucose production is derived from glycogenolysis and half from gluconeogenesis (9,10). Following glucose ingestion, the balance between endogenous glucose production and tissue glucose uptake is disrupted. The increase in plasma glucose concentration stimulates insulin release
1. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus: metabolic and molecular implications for identifying diabetes genes. Diabetes 5:117-269, 1997. 2. Grill V. A comparison of brain glucose metabolism in diabetes as measured by positron emission tomography or by arteriovenous techniques. Ann Med 22:171-175, 1990. 3. DeFronzo RA, Gunnarsson R, Bjorkman O, Olsson M, Wahren J. Effects of insulin on peripheral and splanchnic glucose metabolism in non-insulin dependent diabetes mellitus. J. Clin Invest 76: 149-155, 1985. 4. DeFronzo RA. Lilly Lecture. The triumvirate: beta cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37: 667-687, 1988. 4A. DeFronzo RA. Banting lecture. From the triumvirate to the ominous octet: anew paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58:773-795, 2009 4B. Nauck M, Stockmann F, Ebert R, Creutzfeld W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46-52, 1986

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