ArticleThe Journal of biological chemistry2012
Leucine stimulates insulin secretion via down-regulation of surface expression of adrenergic α2A receptor through the mTOR (mammalian target of rapamycin) pathway: implication in new-onset diabetes in renal transplantation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
- Very high-protein and low-carbohydrate enteral nutrition formula and plasma glucose control in adults with type 2 diabetes mellitus: a randomized crossover trial.Nutrition & diabetes · 2018Trial
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- Plasma metabolite association profiles for type 2 diabetes genetic clusters in Finnish men.Diabetologia · 2026Article
- Emerging Insights into the Liver-Pancreas Axis: A Central Hub in the Pathogenesis of Diabetes and Metabolic Diseases.Biomolecules · 2026Review
- Development of a severe rat refeeding syndrome model and mathematical modeling of the associated hypophosphatemia.NPJ systems biology and applications · 2026Article
- Leucine Mitigates Diabetic Nephropathy via Its Antioxidant Effect and Modulation of TGF-β/SMAD-3 Signalling Pathway in Streptozotocin-Induced Diabetic Rats.Drug design, development and therapy · 2026Article
- Acute Effects of Dietary Protein Consumption on the Postprandial Metabolic Response, Amino Acid Levels and Circulating MicroRNAs in Patients with Obesity and Insulin Resistance.International journal of molecular sciences · 2024Article
- Investigating the Health Implications of Whey Protein Consumption: A Narrative Review of Risks, Adverse Effects, and Associated Health Issues.Healthcare (Basel, Switzerland) · 2024Review
- D-aspartate stimulates growth hormone secretion in wethers.Journal of animal science · 2024Article
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- Congenital Hyperinsulinism and Maple Syrup Urine Disease: A Challenging CombinationJournal of clinical research in pediatric endocrinology · 2023Article
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- Dietary Supplementation with Sea Buckthorn Berry Puree Alters Plasma Metabolomic Profile and Gut Microbiota Composition in Hypercholesterolemia Population.Foods (Basel, Switzerland) · 2022Article
- Metabolomic Analysis of Serum and Tear Samples from Patients with Obesity and Type 2 Diabetes Mellitus.International journal of molecular sciences · 2022Article
- The metabolomic differential plasma profile between dialysates. Pursuing to understand the mechanisms of citrate dialysate clinical benefits.Frontiers in physiology · 2022Article
- Unveiling the Metabolic Effects of Glycomacropeptide.International journal of molecular sciences · 2021Article
- Physiological effects of nutrients on insulin release by pancreatic beta cells.Molecular and cellular biochemistry · 2021Review
- Dietary Protein and Amino Acid Deficiency Inhibit Pancreatic Digestive Enzyme mRNA Translation by Multiple Mechanisms.Cellular and molecular gastroenterology and hepatology · 2021Article
- Amino Acids in Cell Signaling: Regulation and Function.Advances in experimental medicine and biology · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The amino acid leucine is a potent secretagogue, capable of inducing insulin secretion. It also plays an important role in the regulation of mTOR activity, therefore, providing impetus to investigate if a leucine-sensing mechanism in the mTOR pathway is involved in insulin secretion. We found that leucine-induced insulin secretion was inhibited by both the mTOR inhibitor rapamycin as well as the adrenergic α2 receptor agonist clonidine. We also demonstrated that leucine down-regulated the surface expression of adrenergic α2A receptor via activation of the mTOR pathway. The leucine stimulatory effect on insulin secretion was attenuated in diabetic Goto-Kakizaki rats that overexpress adrenergic α2A receptors, confirming the role of leucine in insulin secretion. Thus, our data demonstrate that leucine regulates insulin secretion by modulating adrenergic α2 receptors through the mTOR pathway. The role of the mTOR pathway in metabolic homeostasis led us to a second important finding in this study; retrospective analysis of clinical data showed that co-administration of rapamycin and clonidine was associated with an increased incidence of new-onset diabetes in renal transplantation patients over those receiving rapamycin alone. We believe that inhibition of mTOR by rapamycin along with activation of adrenergic α2 receptors by clonidine represents a double-hit to pancreatic islets that synergistically disturbs glucose homeostasis. This new insight may have important implications for the clinical management of renal transplant patients.
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