Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: a model for weight gain with intensive insulin therapy
Open accessAbstract
A major side effect of insulin treatment of diabetes is weight gain, which limits patient compliance and may pose additional health risks. Although the mechanisms responsible for this weight gain are poorly understood, it has been suggested that there may be a link to the incidence of recurrent episodes of hypoglycemia. Here we present a rodent model of marked weight gain associated with weekly insulin-induced hypoglycemic episodes in the absence of diabetes. Insulin treatment caused a significant increase in both body weight and fat mass, accompanied by reduced motor activity, lowered thermogenesis in response to a cold challenge, and reduced brown fat uncoupling protein mRNA. However, there was no effect of insulin treatment on total food intake nor on hypothalamic neuropeptide Y or proopiomelanocortin mRNA expression, and insulin-treated animals did not become insulin-resistant. Our results suggest that repeated iatrogenic hypoglycemia leads to weight gain, and that such weight gain is associated with a multifaceted deficit in metabolic regulation rather than to a chronic increase in caloric intake.
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A similar sequence of metabolic events, independent of increased food intake, occurs during development of obesity with insulin administration and with a high-GI diet.
“A similar sequence of metabolic events, independent of increased food intake, occurs during development of obesity with insulin administration (65, 120) and with a high-GI diet (45, 93–96).”
From The carbohydrate-insulin model: A physiological perspective on the obesity pandemic (2021) · cites this paper as [120]
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- Authors
- McNay, E. C., Teske, J. A., Kotz, C. M., Dunn-Meynell, A., Levin, B. E., McCrimmon, R. J., & Sherwin, R. S.
- Affiliations
- University at Albany, State University of New York (US)
- University of Arizona (US)
- University of Minnesota (US)
- East Orange VA Medical Center (US)
- University of Dundee (GB)
- Yale University (US)
- Corresponding author
- McNay, Ewan C.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2013-01-15
- Volume
- 304
- Issue
- 2
- Pages
- E131-E138
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC3543569
- OpenAlex
- W2049457334
- Cited by
- 31
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 7 · 2014: 4 · 2013: 2
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK45735, DK20495, R01DK077106, R01DK020495, DK-077106, R01DK053181, P30DK045735)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- insulin-induced hypoglycemia, weight gain, obesity, intensive insulin therapy, diabetes mellitus, recurrent hypoglycemia, fat mass, thermogenesis, brown adipose tissue, uncoupling proteins, motor activity, neuropeptide Y, proopiomelanocortin, dietary intake, insulin resistance, rodent models
- MeSH terms
- Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Administration Schedule, Hyperphagia, Hypoglycemia, Hypoglycemic Agents, Insulin, Insulin Resistance, Male, Obesity, Periodicity, Severity of Illness Index, Time Factors, Weight Gain, Rats, Sprague-Dawley, Rats
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