Acute and chronic effects of insulin on leptin production in humans: Studies in vivo and in vitro

• Published in: Diabetes (New York, N.Y.) Vol. 45; no. 5; pp. 699 - 701
• Main Authors: Kolaczynski, J W, Nyce, M R, Considine, R V, Boden, G, Nolan, J J, Henry, R, Mudaliar, S R, Olefsky, J, Caro, J F
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01-05-1996
• Subjects: Adipocytes - drug effects; Adipocytes - metabolism; Adult; Blood Glucose - metabolism; Cells, Cultured; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - metabolism; Gene Expression - drug effects; Glucose Clamp Technique; Humans; Infusions, Intravenous; Insulin - administration & dosage; Insulin - pharmacology; Kinetics; Leptin; Obesity - blood; Obesity - metabolism; Polymerase Chain Reaction; Protein Biosynthesis; Proteins - drug effects; Reference Values; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Thinness; Time Factors
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.45.5.699

Acute and chronic effects of insulin on leptin production in humans: Studies in vivo and in vitro.
J W Kolaczynski ,
M R Nyce ,
R V Considine ,
G Boden ,
J J Nolan ,
R Henry ,
S R Mudaliar ,
J Olefsky and
J F Caro
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Phildelphia, PA 19107, USA.
Abstract
This study was undertaken to investigate the changes in obesity (OB) gene expression and production of leptin in response
to insulin in vitro and in vivo under euglycemic and hyperglycemic conditions in humans. Three protocols were used: 1) euglycemic
clamp with insulin infusion rates at 40, 120, 300, and 1,200 mU / m / min carried out for up to 5 h performed in 16 normal
lean individuals, 30 obese individuals, and 31 patients with NIDDM; 2) 64-to 72-h hyperglycemic (glucose 12.6 mmol/l) clamp
performed on 5 lean individuals; 3) long-term (96-h) primary culture of isolated abdominal adipocytes in the presence and
absence of 100 nmol/l insulin. Short-term hyperinsulinemia in the range of 80 to > 10,000 microU/ml had no effect on circulating
levels of leptin. During the prolonged hyperglycemic clamp, a rise in leptin was observed during the last 24 h of the study
(P < 0.001). In the presence of insulin in vitro, OB gene expression increased at 72 h (P < 0.01), followed by an increase
in leptin released to the medium (P < 0.001). In summary, insulin does not stimulate leptin production acutely; however, a
long-term effect of insulin on leptin production could be demonstrated both in vivo and in vitro. These data suggest that
insulin regulates OB gene expression and leptin production indirectly, probably through its trophic effect on adipocytes.