The Insulin Response to Oral Glucose in GIP and GLP-1 Receptor Knockout Mice: Review of the Literature and Stepwise Glucose Dose Response Studies in Female Mice
| العنوان: | The Insulin Response to Oral Glucose in GIP and GLP-1 Receptor Knockout Mice: Review of the Literature and Stepwise Glucose Dose Response Studies in Female Mice |
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| المؤلفون: | Bo Ahrén, Yuichiro Yamada, Yutaka Seino |
| المصدر: | Frontiers in Endocrinology, Vol 12 (2021) Frontiers in Endocrinology |
| بيانات النشر: | Frontiers Media S.A., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, endocrine system, insulin, glucose tolerance, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Administration, Oral, Incretin, 030209 endocrinology & metabolism, Gastric Inhibitory Polypeptide, Glucagon-Like Peptide-1 Receptor, Diseases of the endocrine glands. Clinical endocrinology, Receptors, Gastrointestinal Hormone, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Glucagon-Like Peptide 1, Insulin-Secreting Cells, Internal medicine, Insulin Secretion, Animals, Hypoglycemic Agents, Medicine, Receptor, Glucagon-like peptide 1 receptor, Original Research, Mice, Knockout, GIP, business.industry, Insulin, digestive, oral, and skin physiology, Wild type, Glucagon, RC648-665, Mice, Inbred C57BL, Glucose, 030104 developmental biology, Knockout mouse, Female, business, Literature survey, GLP-1, hormones, hormone substitutes, and hormone antagonists, knockout mice, Hormone |
| الوصف: | A key factor for the insulin response to oral glucose is the pro-glucagon derived incretin hormone glucagon-like peptide-1 (GLP-1), together with the companion incretin hormone, glucose-dependent insulinotropic polypeptide (GIP). Studies in GIP and GLP-1 receptor knockout (KO) mice have been undertaken in several studies to examine this role of the incretin hormones. In the present study, we reviewed the literature on glucose and insulin responses to oral glucose in these mice. We found six publications with such studies reporting results of thirteen separate study arms. The results were not straightforward, since glucose intolerance in GIP or GLP-1 receptor KO mice were reported only in eight of the arms, whereas normal glucose tolerance was reported in five arms. A general potential weakness of the published study is that each of them have examined effects of only one single dose of glucose. In a previous study in mice with genetic deletion of both GLP-1 and GIP receptors we showed that these mice have impaired insulin response to oral glucose after large but not small glucose loads, suggesting that the relevance of the incretin hormones may be dependent on the glucose load. To further test this hypothesis, we have now performed a stepwise glucose administration through a gastric tube (from zero to 125mg) in model experiments in anesthetized female wildtype, GLP-1 receptor KO and GIP receptor KO mice. We show that GIP receptor KO mice exhibit glucose intolerance in the presence of impaired insulin response after 100 and 125 mg glucose, but not after lower doses of glucose. In contrast, GLP-1 receptor KO mice have normal glucose tolerance after all glucose loads, in the presence of a compensatory increase in the insulin response. Therefore, based on these results and the literature survey, we suggest that GIP and GLP-1 receptor KO mice retain normal glucose tolerance after oral glucose, except after large glucose loads in GIP receptor KO mice, and we also show an adaptive mechanism in GLP-1 receptor KO mice, which needs to be further examined. |
| اللغة: | English |
| تدمد: | 1664-2392 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::72d468f567c1d81aabda8c1e89c943bdTest https://www.frontiersin.org/articles/10.3389/fendo.2021.665537/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....72d468f567c1d81aabda8c1e89c943bd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16642392 |
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