Insulin increases leptin mRNA expression in abdominal subcutaneous adipose tissue in humans.
Insulin regulates expression and production of leptin in rodents but whether this is also true in humans remains unclear. To test the effects of acute hyperinsulinemia on expression of leptin mRNA in humans, percutaneous needle biopsies of abdominal subcutaneous adipose tissue were performed at baseline and immediately following a 200-min two-step hyperinsulinemic-euglycemic glucose clamp in 16 Pima Indians (8M/8F). Leptin mRNA was quantified by reverse transcription, PCR amplification and expressed relative to actin mRNA. Leptin mRNA levels were higher in women than men (25.6 +/- 1.7 v 16.9 +/- 2.1 relative units, P = 0.003) at baseline. Baseline levels were directly related to percentage body fat (r = 0.54, P = 0. 03) and fasting plasma glucose concentrations (r = 0.57, P = 0.02) and were negatively correlated to glucose disposal at physiologic insulin concentrations (750 +/- 40 pmol/L) during the clamp (r = -0. 51, P = 0.04). Acute hyperinsulinemia (final insulin concentration 11560 +/- 950 pmol/L) increased leptin mRNA levels in 13 of 16 individuals an average of 13% (21.3 +/- 1.7 to 24.2 +/- 1.2 relative units, P = 0.01). Changes in leptin mRNA were directly related to glucose disposal rates during physiologic hyperinsulinemia (r = 0.54, P < 0.04). These results suggest that the expression of leptin mRNA is regulated by insulin in humans, as it is in rodents.
Pratley
R E
RE
Clinical Diabetes and Nutrition Section, Phoenix Epidemiology and Clinical Research Branch, AZ 85016, USA.
Ren
K
K
Milner
M R
MR
Sell
S M
SM
D000005:Abdomen; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D005215:Fasting; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007198:Indians, North American; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D020738:Leptin / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger; D005947:Glucose