Leptin administration improves skeletal muscle insulin responsiveness in diet-induced insulin-resistant rats.
In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal (Con) or a high-fat (HF) diet for 3 or 6 mo. HF rats were then treated with either vehicle (HF), leptin (HF-Lep, 10 mg. kg(-1). day(-1) sc), or food restriction (HF-FR) for 12-15 days. Glucose tolerance and skeletal muscle glucose uptake and transport were significantly impaired in HF compared with Con. Whole body glucose tolerance and rates of insulin-stimulated skeletal muscle glucose uptake and transport in HF-Lep were similar to those of Con and greater than those of HF and HF-FR. The insulin secretory response to either glucose or tolbutamide (a pancreatic beta-cell secretagogue) was not significantly diminished in HF-Lep. Total and plasma membrane skeletal muscle GLUT-4 protein concentrations were similar in Con and HF-Lep and greater than those in HF and HF-FR. The findings suggest that chronic leptin administration reversed a high-fat diet-induced insulin-resistant state, without compromising insulin secretion.
Yaspelkis
B B
BB
Exercise Biochemistry Laboratory, Department of Kinesiology, California State University Northridge, Northridge, California 91330-8287, USA. ben.yaspelkis@csun.edu
Davis
J R
JR
Saberi
M
M
Smith
T L
TL
Jazayeri
R
R
Singh
M
M
Fernandez
V
V
Trevino
B
B
Chinookoswong
N
N
Wang
J
J
Shi
Z Q
ZQ
Levin
N
N
D019325:3-O-Methylglucose / Q000493:pharmacokinetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D002149:Energy Intake / Q000502:physiology; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology
D001786:Blood Glucose; D004041:Dietary Fats; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D019325:3-O-Methylglucose; D006003:Glycogen; D014044:Tolbutamide