ArticleThe Journal of clinical investigation2017
Mechanism for leptin's acute insulin-independent effect to reverse diabetic ketoacidosis.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Effects of Combination Treatment with Leptin and Liraglutide on Glucose Metabolism in Insulin-Dependent Diabetic Mice.International journal of molecular sciences · 2025Article
- History and future of leptin: Discovery, regulation and signaling.Metabolism: clinical and experimental · 2024Review
- Deficiency of Trex1 leads to spontaneous development of type 1 diabetes.Nutrition & metabolism · 2024Article
- Adipokines in glucose and lipid metabolism.Adipocyte · 2023Article
- Adipocyte STAT5 (signal transducer and activator of transcription 5) is not required for glucocorticoid-induced metabolic dysfunction.American journal of physiology. Endocrinology and metabolism · 2023Article
- Article
- Across-species benefits of adrenalectomy on congenital generalized lipoatrophic diabetes: a review.Frontiers in endocrinology · 2023Review
- Protein Tyrosine Phosphatase 1B Deficiency Improves Glucose Homeostasis in Type 1 Diabetes Treated With Leptin.Diabetes · 2022Article
- Plant miR167e-5p promotes 3T3-L1 adipocyte adipogenesis by targeting β-catenin.In vitro cellular & developmental biology. Animal · 2022Article
- Effects of the timing of the initiation of dietary intake on pediatric type 1 diabetes for diabetic ketoacidosis.BMC pediatrics · 2022Article
- Tissue-Specific Effects of Leptin on Glucose and Lipid Metabolism.Endocrine reviews · 2021Review
- Evaluation of adipokines, adiponectin, visfatin, and omentin, in uncomplicated type I diabetes patients before and after treatment of diabetic ketoacidosis.Journal of endocrinological investigation · 2020Article
- Adipose tissue in health and disease.Open biology · 2020Review
- Dissociation of Muscle Insulin Resistance from Alterations in Mitochondrial Substrate Preference.Cell metabolism · 2020Article
- Sodium-glucose cotransporter-2 inhibitors: Understanding the mechanisms for therapeutic promise and persisting risks.The Journal of biological chemistry · 2020Review
- Article
- Leptin Receptors in RIP-CreFrontiers in endocrinology · 2020Article
- Recent advances in understanding the role of leptin in energy homeostasis.F1000Research · 2020Review
- The endocrine function of adipose tissues in health and cardiometabolic disease.Nature reviews. Endocrinology · 2019Review
- S100A9 extends lifespan in insulin deficiency.Nature communications · 2019Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The mechanism by which leptin reverses diabetic ketoacidosis (DKA) is unknown. We examined the acute insulin-independent effects of leptin replacement therapy in a streptozotocin-induced rat model of DKA. Leptin infusion reduced rates of lipolysis, hepatic glucose production (HGP), and hepatic ketogenesis by 50% within 6 hours and were independent of any changes in plasma glucagon concentrations; these effects were abrogated by coinfusion of corticosterone. Treating leptin- and corticosterone-infused rats with an adipose triglyceride lipase inhibitor blocked corticosterone-induced increases in plasma glucose concentrations and rates of HGP and ketogenesis. Similarly, adrenalectomized type 1 diabetic (T1D) rats exhibited decreased rates of lipolysis, HGP, and ketogenesis; these effects were reversed by corticosterone infusion. Leptin-induced decreases in lipolysis, HGP, and ketogenesis in DKA were also nullified by relatively small increases (15 to 70 pM) in plasma insulin concentrations. In contrast, the chronic glucose-lowering effect of leptin in a STZ-induced mouse model of poorly controlled T1D was associated with decreased food intake, reduced plasma glucagon and corticosterone concentrations, and decreased ectopic lipid (triacylglycerol/diacylglycerol) content in liver and muscle. Collectively, these studies demonstrate marked differences in the acute insulin-independent effects by which leptin reverses fasting hyperglycemia and ketoacidosis in a rodent model of DKA versus the chronic pleotropic effects by which leptin reverses hyperglycemia in a non-DKA rodent model of T1D.
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