Acute intravenous leptin infusion increases glucose turnover but not skeletal muscle glucose uptake in ob/ob mice.
Abstract
The mouse ob gene encodes leptin, an adipocyte hormone that regulates body weight and energy expenditure. Leptin has potent metabolic effects on fat and glucose metabolism. A mutation of the ob gene results in mice with severe hereditary obesity and diabetes that can be corrected by treatment with the hormone. In lean mice, leptin acutely increases glucose metabolism in an insulin-independent manner, which could account, at least in part, for some of the antidiabetic effect of the hormone. To investigate further the acute effect of leptin on glucose metabolism in insulin-resistant obese diabetic mice, leptin (40 ng x g(-1) x h(-1)) was administered intravenously for 6 h in C57Bl/6J ob/ob mice. Leptin increased glucose turnover and stimulated glucose uptake in brown adipose tissue (BAT), brain, and heart with no increase in heart rate. A slight increase in all splanchnic tissues was also noticed. Conversely, no increase in skeletal muscle or white adipose tissue (WAT) glucose uptake was observed. Plasma insulin concentration increased moderately but neither glucose, glucagon, thyroid hormones, growth hormone, nor IGF-1 levels were different from phosphate-buffered saline-infused C57Bl/6J ob/ob mice. In addition, leptin stimulated hepatic glucose production, which was associated with increased glucose-6-phosphatase activity. Conversely, PEPCK activity was rather diminished. Interestingly, hepatic insulin receptor substrate (IRS)1-associated phosphatidylinositol 3-kinase activity was slightly elevated, but neither the content of glucose transporter GLUT2 nor the phosphorylation state of the insulin receptor and IRS-1 were changed by acute leptin treatment. Hepatic lipid metabolism was not stimulated during the acute leptin infusion, since the content of triglycerides, glycerol, and citrate was unchanged. These findings suggest that in ob/ob mice, the antidiabetic antiobesity effect of leptin could be the result of a profound alteration of glucose metabolism in liver, BAT, heart, and consequently, glucose turnover. Insulin resistance of skeletal muscle and WAT, while not affected by acute leptin treatment, could also be corrected in the long term and account for some of leptin's antidiabetic effects.
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In ob/ob mice, intravenous leptin increases glucose turnover and stimulates glucose uptake in brown adipose tissue, brain, and heart, but not in skeletal muscle or white adipose tissue.
“In ob/ob mice, i.v. leptin also increased glucose turnover and stimulated glucose uptake in brown adipose tissue (BAT), brain and heart, but not in skeletal muscle or white adipose tissue (WAT) (29).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [29]
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- Authors
- Burcelin, R., Kamohara, S., Li, J., Tannenbaum, G. S., Charron, M. J., & Friedman, J. M.
- Affiliations
- Albert Einstein College of Medicine (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1999-06-01
- Volume
- 48
- Issue
- 6
- Pages
- 1264-1269
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2127314379
- Cited by
- 92
- References
- 13
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2022: 2 · 2021: 2 · 2019: 1 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 2 · 2012: 4
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- leptin, ob/ob mice, glucose turnover, skeletal muscle glucose uptake, hepatic glucose production, glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, insulin resistance, IRS-1, phosphatidylinositol 3-kinase, white adipose tissue, antidiabetic effect, obesity
- MeSH terms
- Animals, Electrocardiography, Female, Glucagon, Gluconeogenesis, Glucose, Heart Rate, Infusions, Intravenous, Insulin, Insulin-Like Growth Factor I, Liver, Mice, Inbred C57BL, Mice, Obese, Obesity, Proteins, Growth Hormone, Muscle, Skeletal, Leptin, Mice
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