Plasma glucose and insulin responses to a muscarinic agonist (bethanechol chloride) and a muscarinic antagonist (atropine) were evaluated in obese C57BL/6J ob/ob mice and in lean C57BL/6J + /? mice. In lean + /? mice, plasma glucose decreased in response to 1 and 2 μg/g bethanechol chloride, whereas insulin increased significantly. In ob/ob mice, insulin increased remarkably in response to bethanechol administration (saline, 632 ± 80 μU/ml; 2 μg/g bethanechol chloride, 1794 ± 97 μU/ml; n = 10), but surprisingly, plasma glucose also rose significantly (saline, 230 ± 14 mg/dl; 2 μg/g bethanechol chloride, 363 ± 18 mg/dl, n = 10). This exaggerated hyperglycemie in ob/ob mice was not associated with significant changes in plasma glucagon. Furthermore, administration of propranolol hydrochloride did not diminish bethanechol chloride-induced hyperglycemia in ob/ob mice. Administration of atropine (2.5, 5, and 10 mg/kg body wt) induced a significant decrease in plasma insulin without changes in plasma glucose in ob/ob mice, whereas neither plasma insulin nor plasma glucose changed in lean mice. Finally, conversion of [14C]alanine to glucose was increased in ob/ob mice after bethanechol chloride administration, indicating that muscarinic stimulation increases gluconeogenesis in an animal model of type II (non-insulin-dependent) diabetes.
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Original Articles|
November 01 1989
Muscarinic Stimulation and Antagonism and Glucoregulation in Nondiabetic and Obese Hyperglycemic Mice
Shin Fukudo;
Shin Fukudo
Departments of Psychiatry, Pharmacology, and Medicine, Duke University Medical Center
Durham, North Carolina
Department of Psychosomatic Medicine, School of Medicine, Tohoku University
Sendei, Japan
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Suzanne Virnelli;
Suzanne Virnelli
Departments of Psychiatry, Pharmacology, and Medicine, Duke University Medical Center
Durham, North Carolina
Department of Psychosomatic Medicine, School of Medicine, Tohoku University
Sendei, Japan
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Cynthia M Kuhn;
Cynthia M Kuhn
Departments of Psychiatry, Pharmacology, and Medicine, Duke University Medical Center
Durham, North Carolina
Department of Psychosomatic Medicine, School of Medicine, Tohoku University
Sendei, Japan
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Christina Cochrane;
Christina Cochrane
Departments of Psychiatry, Pharmacology, and Medicine, Duke University Medical Center
Durham, North Carolina
Department of Psychosomatic Medicine, School of Medicine, Tohoku University
Sendei, Japan
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Mark N Feinglos;
Mark N Feinglos
Departments of Psychiatry, Pharmacology, and Medicine, Duke University Medical Center
Durham, North Carolina
Department of Psychosomatic Medicine, School of Medicine, Tohoku University
Sendei, Japan
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Richard S Surwit
Richard S Surwit
Departments of Psychiatry, Pharmacology, and Medicine, Duke University Medical Center
Durham, North Carolina
Department of Psychosomatic Medicine, School of Medicine, Tohoku University
Sendei, Japan
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Address correspondence and reprint requests to Richard S. Surwit, Box 3842, Duke University Medical Center, Durham, NC 27710.
Diabetes 1989;38(11):1433–1438
Article history
Received:
April 17 1989
Revision Received:
July 10 1989
Accepted:
July 10 1989
PubMed:
2576006
Citation
Shin Fukudo, Suzanne Virnelli, Cynthia M Kuhn, Christina Cochrane, Mark N Feinglos, Richard S Surwit; Muscarinic Stimulation and Antagonism and Glucoregulation in Nondiabetic and Obese Hyperglycemic Mice. Diabetes 1 November 1989; 38 (11): 1433–1438. https://doi.org/10.2337/diab.38.11.1433
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