Genetic manipulation of insulin signaling, action and secretion in mice. Insights into glucose homeostasis and pathogenesis of type 2 diabetes.
Non-insulin-dependent diabetes mellitus (NIDDM) is a complex heterogeneous polygenic disease characterized mainly by insulin resistance and pancreatic beta-cell dysfunction. In recent years, several genetically engineered mouse models have been developed for the study of the pathophysiological consequences of defined alterations in a single gene or in a set of candidate diabetogenes. These represent new tools that are providing invaluable insights into NIDDM pathogenesis. In this review, we highlight the lessons emerging from the study of some of the transgenic or knockout mice in which the expression of key actors in insulin signaling, action or secretion has been manipulated. In addition to contributing to our knowledge of the specific roles of individual genes in the control of glucose homeostasis, these studies have made it possible to address several crucial issues in NIDDM that have remained controversial or unanswered for a number of years.
Baudry
Anne
A
Department of Genetics, Development and Molecular Pathology, Institut Cochin, INSERM, CNRS, Université René Descartes, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France.
Leroux
Loïc
L
Jackerott
Malene
M
Joshi
Rajiv L
RL
D000818:Animals; D030801:Animals, Genetically Modified; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins; D010750:Phosphoproteins / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D015221:Potassium Channels; C495693:Slc2a4 protein, mouse; D005947:Glucose