Article
Licensed
Unlicensed
Requires Authentication
Knockout Mice Challenge Our Concepts of Glucose Homeostasis and the Pathogenesis of Diabetes Mellitus
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
-
С. Ronald Kahn
Published/Copyright:
July 22, 2014
ABSTRACT
The failure of insulin to stimulate muscle glucose uptake and suppress hepatic glucose production represents two of the fundamental pathophysiologic lesions in type 2 diabetes mellitus (DM). Defining insulin action at the molecular level, therefore, provides the critical background against which to elucidate the mechanisms of insulin resistance that underlie type 2 DM, obesity and many other disorders. Over the past two decades substantial progress has been made in identifying many of the molecular mechanisms involved in insulin signaling. Much of this progress has been due to the use of homologous recombinant gene targeting. The present review examines the various insights that have been provided by studies of knockout mice strains. Taken together, the results present the possibility of a unifying hypothesis for type 2 DM, in which insulin resistance in the ß-cell synergizes with insulin resistance in the periphery to produce the two classic defects of this disease: relative hypoinsulinemia and peripheral insulin resistance.
Keywords: diabetes mellitus; glucose homeostasis; insulin action; insulin receptors; insulin receptor substrates; insulin resistance; phosphatidylinositol 3-kinase
Published Online: 2014-07-22
Published in Print: 2000-12-01
© 2014 by Walter de Gruyter Berlin/Boston
You are currently not able to access this content.
You are currently not able to access this content.
Articles in the same Issue
- Titelei
- TABLE OF CONTENTS
- Foreword
- What Happens When Growth Hormone is Discontinued at Completion of Growth? Metabolic Aspects
- Growth Hormone Deficiency and Peak Bone Mass
- Optimal Strategy for Management of Pituitary Disease in the Growth Hormone-Deficient Teenager
- Ethical Dilemmas in Pediatric Endocrinology: Growth Hormone for Short Normal Children
- Evidence-Based Approach to Growth Hormone Replacement Therapy in Adults, with Special Emphasis on Body Composition
- Evidence-Based Growth Hormone Therapy Prediction Models
- New Paradigms for Growth Hormone Treatment in the 21st Century: Prediction Models
- Role of Insulin-like Growth Factor Monitoring in Optimizing Growth Hormone Therapy
- Knockout Mice Challenge Our Concepts of Glucose Homeostasis and the Pathogenesis of Diabetes Mellitus
- Type 2 Diabetes Mellitus in Children: Pathophysiology and Risk Factors
- Emergence of Type 2 Diabetes Mellitus in Children: Epidemiological Evidence
- Treatment of Type 2 Diabetes Mellitus in Children and Adolescents
- Diagnosis of Maturity-Onset Diabetes of the Young in the Pediatric Diabetes Clinic
- Thrifty Genotypes and Phenotypes in the Pathogenesis of Type 2 Diabetes Mellitus
- Estradiol: A Protective Factor in the Adult Brain
- Estrogen Treatment and Estrogen Suppression: Metabolic Effects in Adolescence
- Estrogen, Bone, Growth and Sex: A Sea Change in Conventional Wisdom
- Route-Dependent Endocrine and Metabolic Effects of Estrogen Replacement Therapy
- Telomerase and the Cellular Lifespan: Implications for the Aging Process
- Human Aging and Progeria
- A Role for the Somatotropic Axis in Neural Development, Injury and Disease
- Hypothalamic Growth Hormone-Insulin-like Growth Factor-I Axis across the Human Life Span
- The Lost Voice: A History of the Castrato
- SELECTED POSTER ABSTRACTS
- GROWTH. FETAL GROWTH. SGA
- SYNDROMES: TURNER. PRADER-WILLI. NOONAN. PHP. OTHERS
- GHD. HYPOPITUITARISM. KIGS
- METABOLIC. GENETIC. ADULT. ACROMEGALY
- GH. IGF. IGFBPs
- GROWTH IN SYSTEMIC DISEASE. CRI. RICKETS. STEROIDS
Keywords for this article
diabetes mellitus;
glucose homeostasis;
insulin action;
insulin receptors;
insulin receptor substrates;
insulin resistance;
phosphatidylinositol 3-kinase
Articles in the same Issue
- Titelei
- TABLE OF CONTENTS
- Foreword
- What Happens When Growth Hormone is Discontinued at Completion of Growth? Metabolic Aspects
- Growth Hormone Deficiency and Peak Bone Mass
- Optimal Strategy for Management of Pituitary Disease in the Growth Hormone-Deficient Teenager
- Ethical Dilemmas in Pediatric Endocrinology: Growth Hormone for Short Normal Children
- Evidence-Based Approach to Growth Hormone Replacement Therapy in Adults, with Special Emphasis on Body Composition
- Evidence-Based Growth Hormone Therapy Prediction Models
- New Paradigms for Growth Hormone Treatment in the 21st Century: Prediction Models
- Role of Insulin-like Growth Factor Monitoring in Optimizing Growth Hormone Therapy
- Knockout Mice Challenge Our Concepts of Glucose Homeostasis and the Pathogenesis of Diabetes Mellitus
- Type 2 Diabetes Mellitus in Children: Pathophysiology and Risk Factors
- Emergence of Type 2 Diabetes Mellitus in Children: Epidemiological Evidence
- Treatment of Type 2 Diabetes Mellitus in Children and Adolescents
- Diagnosis of Maturity-Onset Diabetes of the Young in the Pediatric Diabetes Clinic
- Thrifty Genotypes and Phenotypes in the Pathogenesis of Type 2 Diabetes Mellitus
- Estradiol: A Protective Factor in the Adult Brain
- Estrogen Treatment and Estrogen Suppression: Metabolic Effects in Adolescence
- Estrogen, Bone, Growth and Sex: A Sea Change in Conventional Wisdom
- Route-Dependent Endocrine and Metabolic Effects of Estrogen Replacement Therapy
- Telomerase and the Cellular Lifespan: Implications for the Aging Process
- Human Aging and Progeria
- A Role for the Somatotropic Axis in Neural Development, Injury and Disease
- Hypothalamic Growth Hormone-Insulin-like Growth Factor-I Axis across the Human Life Span
- The Lost Voice: A History of the Castrato
- SELECTED POSTER ABSTRACTS
- GROWTH. FETAL GROWTH. SGA
- SYNDROMES: TURNER. PRADER-WILLI. NOONAN. PHP. OTHERS
- GHD. HYPOPITUITARISM. KIGS
- METABOLIC. GENETIC. ADULT. ACROMEGALY
- GH. IGF. IGFBPs
- GROWTH IN SYSTEMIC DISEASE. CRI. RICKETS. STEROIDS
