The Mechanism of Hypoglycemia Due to Semistarvation in the Rat
Abstract
A quantity of diet providing 50% of the energy and protein requirement was fed to 4 week old rats. After 3 weeks, the amount of food was reduced to 25% and resulted in hypoglycemia in most of the rats within 4 to 7 days. The rats were divided into three groups: 1) normal controls; 2) malnourished, exhibiting blood sugar levels more than 40 mg/100 ml; 3) malnourished with blood sugar concentration less than 40 mg/100ml. The plasma concentrations of energy providing substrates: free fatty acids, glycerol, pyruvic acid, lactic acid and alanine were significantly lower in the hypoglycemic group than in the other two groups, while the first two groups displayed no significant differences. Plasma insulin concentrations were reduced in the undernourished groups and the lowest levels were found in the hypoglycemic rats. The plasma corticosterone concentration was significantly greater in group 2 but only slightly higher in group 3 than in the controls. Blood glucose concentration did not increase after intravenous glucagon in group 3, but the response was restored 4 hours after glucose administration. Blood glucose did not increase after alanine infusion in group 3 and increased only moderately in group 2. There was a normal increase after glycerol infusion in both malnourished groups. It was concluded that in semistarvation, fatal hypoglycemia is due to the depletion of fat stores accompanied by impaired gluconeogenesis from alanine.
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Gluconeogenesis is disrupted by malnutrition due to hepatic glucagon resistance and decreased availability of gluconeogenic substrates including lactate, glycerol, and alanine.
“Gluconeogenesis is another physiologic pathway that is disrupted by malnutrition. This results from hepatic glucagon resistance and decreased availability of gluconeogenic substrates, including lactate, glycerol, and alanine [14].”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [14]
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Non-Diabetic Hypoglycemia: Evaluation and Management in Adults
Looi, E., & Lawler, H. M. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134393 · Cited by 10 · see citing works
- Authors
- Gács, G.
- Affiliations
- Semmelweis University (HU)
- Corresponding author
- Gács, Gábor
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 1976-11
- Volume
- 106
- Issue
- 11
- Pages
- 1557-1561
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W1593955423
- Cited by
- 8
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- hypoglycemia, semistarvation, malnutrition, gluconeogenesis, alanine, fat stores, plasma insulin, corticosterone, glucagon response, glycerol infusion, free fatty acids, lactic acid, pyruvate, blood glucose
- MeSH terms
- Alanine, Animals, Blood Glucose, Disease Models, Animal, Energy Metabolism, Glucagon, Glucose, Glycerol, Hypoglycemia, Male, Protein-Energy Malnutrition, Lipid Metabolism, Rats
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