Evidence for time dependent variation of glucagon secretion in mice |
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| Affiliation: | 1. School of Medicine, Dentistry and Biomedical Sciences, The Queen’s University of Belfast, Northern Ireland, UK;2. Peterborough City Hospital, Peterborough, England, UK;3. Hillingdon Hospitals NHS Trust, London, England, UK;4. Southeastern Health and Social Care Trust, Northern Ireland, UK;5. Belfast Health and Social Care Trust, Belfast City Hospital, Northern Ireland, UK;1. Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, China;2. Department of Respiratory Medicine, Kunming General Hospital of Chengdu Military Command, Kunming, China;3. Department of Respiratory Medicine, Pudong New Area Gongli Hospital, Shanghai, China;4. Institute of Field Internal Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China;5. Department of Respiratory Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;1. Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;2. Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;3. Okayama University Hospital, Okayama, Japan;1. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Bari, 70124, Italy;2. IRCCS “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, 71013, Italy;3. Department of Psychosis Studies, Institute of Psychiatry, Neurology and Neuroscience, King’s College, London, WC2R 2LS, UK;4. Department of Medicine, University of Perugia, 06132, Italy |
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| Abstract: | Glucose metabolism is subjected to diurnal variation, which might be mediated by alterations in the transcription pattern of clock genes and regulated by hormonal factors, as has been demonstrated for insulin. However, whether also glucagon is involved in the diurnal variation of glucose homeostasis is not known. We therefore examined glucagon secretion after meal ingestion (meal tolerance test) and during hypoglycemia (hyperinsulinemic hypoglycemic clamp at 2.5 mmol/L glucose) and in vitro from isolated islets at ZT3 versus ZT15 in normal C57BL/6J mice and, furthermore, glucose levels and the insulin response to meal ingestion were also examined at these time points in glucagon receptor knockout mice (GCGR−/−) and their wildtype (wt) littermates.We found in normal mice that whereas the glucagon response to meal ingestion was not different between ZT3 and ZT15, the glucagon response to hypoglycemia was lower at ZT3 than at ZT15 and glucagon secretion from isolated islets was higher at ZT3 than at ZT15. GCGR−/− mice displayed lower basal glucose, a lower insulin response to meal and a higher insulin sensitivity than wt mice at ZT3 but not at ZT15. We conclude that there is a time dependent variation in glucagon secretion in normal mice, which is dependent both on intraislet and extraislet regulatory mechanisms and that the phenotype characteristics of a lower glucose and reduced insulin response to meal in GCGR−/− mice are evident only during the light phase. These findings suggest that glucagon signaling is a plausible contributor to the diurnal variation in glucose homeostasis which may explain that the phenotype of the GCGR−/− mice is dependent on the time of the day when it is examined. |
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| Keywords: | Glucagon Glucose Oscillation Time dependency Hypoglycemia Mice |
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