ArticleEndocrinology2014
Role of melanocortin signaling in neuroendocrine and metabolic actions of leptin in male rats with uncontrolled diabetes.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Development and characterization of an Sf-1-Flp mouse model.JCI insight · 2025Article
- Development and Characterization of abioRxiv : the preprint server for biology · 2025Article
- Type 2 Diabetes Remission in Patients with Heterozygous Variants in the Leptin-Melanocortin Pathway after Roux-en-Y Gastric Bypass: A Matched Case-Control Study.Obesity surgery · 2023Article
- AgRP neurons: Regulators of feeding, energy expenditure, and behavior.The FEBS journal · 2022Review
- A neural basis for brain leptin action on reducing type 1 diabetic hyperglycemia.Nature communications · 2021Article
- Glucose-Lowering by Leptin in the Absence of Insulin Does Not Fully Rely on the Central Melanocortin System in Male Mice.Endocrinology · 2019Article
- Article
- In Uncontrolled Diabetes, Hyperglucagonemia and Ketosis Result From Deficient Leptin Action in the Parabrachial Nucleus.Endocrinology · 2018Article
- Peripheral cannabinoid-1 receptor blockade restores hypothalamic leptin signaling.Molecular metabolism · 2017Article
- The Determinants of Leptin Levels in Diabetic and Nondiabetic Saudi Males.International journal of endocrinology · 2017Article
- The role of leptin in diabetes: metabolic effects.Diabetologia · 2016Review
- Pleotropic effects of leptin to reverse insulin resistance and diabetic ketoacidosis.Diabetologia · 2016Review
- Euglycemia Restoration by Central Leptin in Type 1 Diabetes Requires STAT3 Signaling but Not Fast-Acting Neurotransmitter Release.Diabetes · 2016Article
- The functional activity of hypothalamic signaling systems in rats with neonatal diabetes mellitus treated with metformin.Doklady. Biochemistry and biophysics · 2016Article
- Brain signaling systems in the Type 2 diabetes and metabolic syndrome: promising target to treat and prevent these diseases.Future science OA · 2015Review
- Brain-mediated antidiabetic, anorexic, and cardiovascular actions of leptin require melanocortin-4 receptor signaling.Journal of neurophysiology · 2015Article
- Leptin recruits Creb-regulated transcriptional coactivator 1 to improve hyperglycemia in insulin-deficient diabetes.Molecular metabolism · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Although the antidiabetic effects of leptin require intact neuronal melanocortin signaling in rodents with uncontrolled diabetes (uDM), increased melanocortin signaling is not sufficient to mimic leptin's glucose-lowering effects. The current studies were undertaken to clarify the role of melanocortin signaling in leptin's ability to correct metabolic and neuroendocrine disturbances associated with uDM. To accomplish this, bilateral cannulae were implanted in the lateral ventricle of rats with streptozotocin-induced diabetes, and leptin was coinfused with varying doses of the melanocortin 3/4 receptor (MC3/4R) antagonist, SHU9119. An additional cohort of streptozotocin-induced diabetes rats received intracerebroventricular administration of either the MC3/4R agonist, melanotan-II, or its vehicle. Consistent with previous findings, leptin's glucose-lowering effects were blocked by intracerebroventricular SHU9119. In contrast, leptin-mediated suppression of hyperglucagonemia involves both melanocortin dependent and independent mechanisms, and the degree of glucagon inhibition was associated with reduced plasma ketone body levels. Increased central nervous system melanocortin signaling alone fails to mimic leptin's ability to correct any of the metabolic or neuroendocrine disturbances associated with uDM. Moreover, the inability of increased melanocortin signaling to lower diabetic hyperglycemia does not appear to be secondary to release of the endogenous MC3/4R inverse agonist, Agouti-related peptide (AgRP), because AgRP knockout mice did not show increased susceptibility to the antidiabetic effects of increased MC3/4R signaling. Overall, these data suggest that 1) AgRP is not a major driver of diabetic hyperglycemia, 2) mechanisms independent of melanocortin signaling contribute to leptin's antidiabetic effects, and 3) melanocortin receptor blockade dissociates leptin's glucose-lowering effect from its action on other features of uDM, including reversal of hyperglucagonemia and ketosis, suggesting that brain control of ketosis, but not blood glucose levels, is glucagon dependent.
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