ArticleAmerican journal of physiology. Endocrinology and metabolism2012
Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice.
Article in American journal of physiology. Endocrinology and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Germline and conditional ghrelin knockout increases islet size.The Journal of clinical investigation · 2023Article
- Ghrelin deletion and conditional ghrelin cell ablation increase pancreatic islet size in mice.The Journal of clinical investigation · 2023Article
- The expression and function of growth hormone secretagogue receptor in immune cells: A current perspective.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Mechanistic Investigation of GHS-R Mediated Glucose-Stimulated Insulin Secretion in Pancreatic Islets.Biomolecules · 2022Article
- LEAP-2 Counteracts Ghrelin-Induced Food Intake in a Nutrient, Growth Hormone and Age Independent Manner.Cells · 2022Article
- β Cell GHS-R Regulates Insulin Secretion and Sensitivity.International journal of molecular sciences · 2021Article
- "A LEAP 2 conclusions? Targeting the ghrelin system to treat obesity and diabetes".Molecular metabolism · 2021Review
- Ghrelin Receptor Signaling Is Not Required for Glucocorticoid-Induced Obesity in Male Mice.Endocrinology · 2020Article
- Article
- Incretin dysfunction and hyperglycemia in cystic fibrosis: Role of acyl-ghrelin.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2019Article
- Ghrelin regulation of glucose metabolism.Journal of neuroendocrinology · 2019Review
- Ghrelin's Relationship to Blood Glucose.Endocrinology · 2019Review
- Long-term treatment with the ghrelin receptor antagonist [d-Lys3]-GHRP-6 does not improve glucose homeostasis in nonobese diabetic MKR mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Oncology Update: Anamorelin.Palliative care · 2017Review
- The effect of ghrelin on Kiss-1 and KissR gene transcription and insulin secretion in rat islets of Langerhans and CRI-D2 cell line.Iranian journal of basic medical sciences · 2017Article
- Article
- Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases.Endocrine · 2015Review
- Assessing interactions between Ghsr and Mc3r reveals a role for AgRP in the expression of food anticipatory activity in male mice.Endocrinology · 2014Article
- Interrelationships between ghrelin, insulin and glucose homeostasis: Physiological relevance.World journal of diabetes · 2014Review
- Gastric bypass surgery may improve beta cell apoptosis with ghrelin overexpression in patients with BMI ≥ 32.5 kg/m(2.).Obesity surgery · 2014Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion. Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia. The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes. However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion. We investigated the effects of GHS-R on glucose homeostasis in Ghsr-ablated ob/ob mice (Ghsr(-/-):ob/ob). Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice. Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance. Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency. Of note, Ghsr ablation in ob/ob mice did not affect the islet size; the average islet size of Ghsr(-/-):ob/ob mice is similar to that of ob/ob mice. In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions. The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.