Cited by 198Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesGrowth Hormone and Insulin-like Growth Factors

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Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin

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Havel, Peter J., Uriu-Hare, Janet Y., Liu, Tina, Stanhope, Kimber L., Stern, Judith S., Keen, Carl L., Ahrén, Bo·1998·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

DOI 10.1152/ajpregu.1998.274.5.r1482

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Abstract

Evidence for regulation of circulating leptin by insulin is conflicting. Diabetes was induced in rats with streptozotocin (STZ; 40 mg ⋅ kg−1⋅ day−1× 2 days) to examine the effect of insulin-deficient diabetes and insulin treatment on circulating leptin. After 12 wk, plasma leptin concentrations in untreated rats were all <0.4 ng/ml versus 4.9 ± 0.9 ng/ml in control animals ( P < 0.005). In rats treated with subcutaneous insulin implants for 12 wk, which reduced hyperglycemia by ∼50%, plasma leptin was 2.1 ± 0.6 ng/ml, whereas leptin concentrations were 6.0 ± 1.6 ng/ml in insulin-implanted rats receiving supplemental injections of insulin for 4 days to normalize plasma glucose ( P< 0.005 vs. STZ untreated). In a second experiment, plasma leptin was monitored at biweekly intervals during 12 wk of diabetes. In rats treated with insulin implants, plasma leptin concentrations were inversely proportional to glycemia ( r= −0.64; P < 0.0001) and unrelated to body weight ( P = 0.40). In a third experiment, plasma leptin concentrations were examined very early after the induction of diabetes. Within 24 h after STZ injection, plasma insulin decreased from 480 ± 30 to 130 ± 10 pM ( P < 0.0001), plasma glucose increased from 7.0 ± 0.2 to 24.8 ± 0.5 mM, and plasma leptin decreased from 3.2 ± 0.2 to 1.2 ± 0.1 ng/ml (Δ = −63 ± 3%, P < 0.0001). In a subset of diabetic rats treated with insulin for 2 days, glucose decreased to 11.7 ± 3.9 mM and leptin increased from 0.5 ± 0.1 to 2.9 ± 0.6 ng/ml ( P< 0.01) without an effect on epididymal fat weight. The change of leptin was correlated with the degree of glucose lowering ( r = 0.75, P < 0.05). Thus insulin-deficient diabetes produces rapid and sustained decreases of leptin that are not solely dependent on weight loss, whereas insulin treatment reverses the hypoleptinemia. We hypothesize that decreased glucose transport into adipose tissue may contribute to decreased leptin production in insulin-deficient diabetes.

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Authors: Havel, P. J., Uriu-Hare, J. Y., Liu, T., Stanhope, K. L., Stern, J. S., Keen, C. L., & Ahrén, B.
Affiliations: Lund University (SE)
Department of Nutrition, University of California, Davis, California 95616; and Department of Medicine, Lund University, S-20502 Malmö, Sweden
ORCID: Havel, Peter J.
Liu, Tina
Stanhope, Kimber L.
Keen, Carl L.
Venue: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Publisher: American Physiological Society
Published: 1998-05-01
Volume: 274
Issue: 5
Pages: R1482-R1491
ISSN: 0363-6119 (ISSN-L)
1522-1490
DOI: 10.1152/ajpregu.1998.274.5.r1482
OpenAlex: W2112457773
Cited by: 198
References: 45
Citations by year: 2024: 2 · 2023: 4 · 2021: 8 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 1 · 2016: 8 · 2015: 13 · 2014: 7 · 2013: 10 · 2012: 10
FWCI: 4.84
Type: journal article
Language: en
Open access: green
escholarship.org
Locations: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health (5r01dk018899-18)
Medical Research Council
National Cancer Institute
National Institute of Diabetes and Digestive and Kidney Diseases (DK-07355, T32DK007355, DK 50129, R01DK050129, DK-18899)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords: leptin, insulin, streptozotocin-induced diabetes, insulin deficiency, insulin therapy, plasma leptin concentration, glycemia, hyperglycemia, leptin regulation, insulin resistance, epididymal adipose tissue, body weight, diabetes reversal, leptin resistance, adipose tissue, energy homeostasis, rats, mice
MeSH terms: Animals, Blood Glucose, Body Weight, Diabetes Mellitus, Experimental, Eating, Hypoglycemic Agents, Insulin, Male, Proteins, Streptozocin, Rats, Sprague-Dawley, Leptin, Rats

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Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin

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