ArticleDiabetes2015
Evidence That in Uncontrolled Diabetes, Hyperglucagonemia Is Required for Ketosis but Not for Increased Hepatic Glucose Production or Hyperglycemia.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Efficacy and safety of dual SGLT 1/2 inhibitor sotagliflozin in type 1 diabetes: meta-analysis of randomised controlled trials.BMJ (Clinical research ed.) · 2019Pooled it
- Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1 Diabetes: The North American inTandem1 Study.Diabetes care · 2018Trial
- Prurigo pigmentosa in patient with diabetes on SGLT2 inhibitor.JAAD case reports · 2026Article
- AgRP neuron hyperactivity drives hyperglycemia in a mouse model of type 2 diabetes.The Journal of clinical investigation · 2025Article
- The impact of glucagon to support postabsorptive glucose flux and glycemia in healthy rats and its attenuation in male Zucker diabetic fatty rats.American journal of physiology. Endocrinology and metabolism · 2024Article
- The past, present, and future physiology and pharmacology of glucagon.Cell metabolism · 2022Review
- Glucagon, cyclic AMP, and hepatic glucose mobilization: A half-century of uncertainty.Physiological reports · 2022Review
- Chronic Antidiabetic Actions of Leptin: Evidence From Parabiosis Studies for a CNS-Derived Circulating Antidiabetic Factor.Diabetes · 2021Article
- Glucagon's Metabolic Action in Health and Disease.Comprehensive Physiology · 2021Article
- Insulin on changes in expressions of aquaporin-1, aquaporin-5, and aquaporin-8 in submandibular salivary glands of rats with Streptozotocin-induced diabetes.International journal of clinical and experimental pathology · 2021Article
- CNS Regulation of Glucose Homeostasis: Role of the Leptin-Melanocortin System.Current diabetes reports · 2020Review
- UCP1-independent glucose-lowering effect of leptin in type 1 diabetes: only in conditions of hypoleptinemia.American journal of physiology. Endocrinology and metabolism · 2020Article
- Peripheral Mechanisms Mediating the Sustained Antidiabetic Action of FGF1 in the Brain.Diabetes · 2019Article
- A New Way for Beta Cell Neogenesis: Transdifferentiation from Alpha Cells Induced by Glucagon-Like Peptide 1.Journal of diabetes research · 2019Article
- In Uncontrolled Diabetes, Hyperglucagonemia and Ketosis Result From Deficient Leptin Action in the Parabrachial Nucleus.Endocrinology · 2018Article
- Newer Perspectives of Mechanisms for Euglycemic Diabetic Ketoacidosis.International journal of endocrinology · 2018Article
- Lipid nanoparticle delivery of glucagon receptor siRNA improves glucose homeostasis in mouse models of diabetes.Molecular metabolism · 2017Article
- Insulin and Glucagon: Partners for Life.Endocrinology · 2017Review
- How does leptin restore euglycemia in insulin-deficient diabetes?The Journal of clinical investigation · 2017Article
- Glucagon receptor gene deletion in insulin knockout mice modestly reduces blood glucose and ketones but does not promote survival.Molecular metabolism · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Several lines of evidence implicate excess glucagon secretion in the elevated rates of hepatic glucose production (HGP), hyperglycemia, and ketosis characteristic of uncontrolled insulin-deficient diabetes (uDM), but whether hyperglucagonemia is required for hyperglycemia in this setting is unknown. To address this question, adult male Wistar rats received either streptozotocin (STZ) to induce uDM (STZ-DM) or vehicle and remained nondiabetic. Four days later, animals received daily subcutaneous injections of either the synthetic GLP-1 receptor agonist liraglutide in a dose-escalating regimen to reverse hyperglucagonemia or its vehicle for 10 days. As expected, plasma glucagon levels were elevated in STZ-DM rats, and although liraglutide treatment lowered glucagon levels to those of nondiabetic controls, it failed to attenuate diabetic hyperglycemia, elevated rates of glucose appearance (Ra), or increased hepatic gluconeogenic gene expression. In contrast, it markedly reduced levels of both plasma ketone bodies and hepatic expression of the rate-limiting enzyme involved in ketone body production. To independently confirm this finding, in a separate study, treatment of STZ-DM rats with a glucagon-neutralizing antibody was sufficient to potently lower plasma ketone bodies but failed to normalize elevated levels of either blood glucose or Ra. These data suggest that in rats with uDM, hyperglucagonemia is required for ketosis but not for increased HGP or hyperglycemia.
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