Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle.
Obesity and insulin resistance in skeletal muscle are two major factors in the pathogenesis of type 2 diabetes. Mice with muscle-specific inactivation of the insulin receptor gene (MIRKO) are normoglycemic but have increased fat mass. To identify the potential mechanism for this important association, we examined insulin action in specific tissues of MIRKO and control mice under hyperinsulinemic-euglycemic conditions. We found that insulin-stimulated muscle glucose transport and glycogen synthesis were decreased by about 80% in MIRKO mice, whereas insulin-stimulated fat glucose transport was increased threefold in MIRKO mice. These data demonstrate that selective insulin resistance in muscle promotes redistribution of substrates to adipose tissue thereby contributing to increased adiposity and development of the prediabetic syndrome.
Kim
J K
JK
Department of Internal Medicine and the Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
Michael
M D
MD
Previs
S F
SF
Peroni
O D
OD
Mauvais-Jarvis
F
F
Neschen
S
S
Kahn
B B
BB
Kahn
C R
CR
Shulman
G I
GI
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000096:biosynthesis; D006019:Glycolysis; D006946:Hyperinsulinism; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D011972:Receptor, Insulin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D006003:Glycogen; D011972:Receptor, Insulin; D005947:Glucose