Free fatty acid receptor 3 differentially contributes to β-cell compensation under high-fat diet and streptozotocin stress
| Autor: | Brian T. Layden, Congcong He, Anton E. Ludvik, Gautham Oroskar, Medha Priyadarshini, Connor Cole, Barton Wicksteed |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine medicine.medical_specialty Genotype Physiology Cell Apoptosis Diet High-Fat Diabetes Mellitus Experimental Receptors G-Protein-Coupled Mice 03 medical and health sciences 0302 clinical medicine Insulin-Secreting Cells Physiology (medical) Internal medicine Diabetes mellitus Autophagy medicine Free fatty acid receptor 3 Animals Cell Proliferation geography geography.geographical_feature_category Chemistry Glucose Tolerance Test Islet Streptozotocin medicine.disease 030104 developmental biology medicine.anatomical_structure Endocrinology Gene Expression Regulation Basal (medicine) 030220 oncology & carcinogenesis Glucose Clamp Technique Insulin Resistance Food Deprivation Ex vivo Research Article medicine.drug |
| Zdroj: | Am J Physiol Regul Integr Comp Physiol |
| ISSN: | 1522-1490 0363-6119 |
| Popis: | The free fatty acid receptor 3 (FFA3) is a nutrient sensor of gut microbiota-generated nutrients, the short-chain fatty acids. Previously, we have shown that FFA3 is expressed in β-cells and inhibits islet insulin secretion ex vivo. Here, we determined the physiological relevance of the above observation by challenging wild-type (WT) and FFA3 knockout (KO) male mice with 1) hyperglycemia and monitoring insulin response via highly sensitive hyperglycemic clamps, 2) dietary high fat (HF), and 3) chemical-induced diabetes. As expected, FFA3 KO mice exhibited significantly higher insulin secretion and glucose infusion rate in hyperglycemic clamps. Predictably, under metabolic stress induced by HF-diet feeding, FFA3 KO mice exhibited less glucose intolerance compared with the WT mice. Moreover, similar islet architecture and β-cell area in HF diet-fed FFA3 KO and WT mice was observed. Upon challenge with streptozotocin (STZ), FFA3 KO mice initially exhibited a tendency for an accelerated incidence of diabetes compared with the WT mice. However, this difference was not maintained. Similar glycemia and β-cell mass loss was observed in both genotypes 10 days post-STZ challenge. Higher resistance to STZ-induced diabetes in WT mice could be due to higher basal islet autophagy. However, this difference was not protective because in response to STZ, similar autophagy induction was observed in both WT and FFA3 KO islets. These data demonstrate that FFA3 plays a role in modulating insulin secretion and β-cell response to stressors. The β-cell FFA3 and autophagy link warrant further research. |
| Databáze: | OpenAIRE |
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