Defective glucagon secretion during hypoglycemia is characteristic of long-standing type I diabetes. To determine whether this defect can be corrected by successful intrahepatic islet transplantation, we performed studies of hypoglycemia in four nondiabetic patients with chronic pancreatitis who had undergone total pancreatectomy and successful intrahepatic islet autotransplantation, in two type I diabetic recipients of successful intrahepatic islet allotransplantation, and in matched control subjects. We examined 1) whether intrahepatic islet autotransplantation provides glucagon secretion during prolonged periods of hypoglycemia and 2) whether intrahepatic islet allotransplantation in type I diabetic patients and consequent long-term normoglycemia reestablishes native α-cell responses to hypoglycemia. Glucagon secretion was assessed during 3-h hypoglycemic hyperinsulinemic clamp studies. The islet autograft recipients were studied 63 ± 19 months posttransplant, and all were insulinindependent and normoglycemic (HbA1c, 5.8 ±± 0.2%). Neither allograft recipient required exogenous insulin and maintained HbA1c levels of 5.7 and 6.4% 30 and 34 months posttransplant, respectively. All recipients were normoglycemic (fasting glucose: autograft recipients, 5.6 ± 0.1 mmol/l; allograft recipient #1, 6.3 mmol/l; allograft recipient #2, 5.8 mmol/l) at the time of study. During hypoglycemia, no increase in glucagon secretion was observed in either the auto- or allotransplant recipients, whereas healthy control subjects and recipients of kidney transplantation had significant increases in glucagon. In contrast, both allo- and autograft recipients had glucagon responses to intravenous arginine. These data uniquely demonstrate that: 1) intrahepatic islet transplant grafts secrete glucagon in response to arginine, but fail to secrete glucagon in response to sustained hypoglycemia; and 2) the restoration of sustained normoglycemia for over 2 years in type I diabetic patients may not reestablish glucagon responses from the native pancreas during hypoglycemia. Transplantation sites other than the liver may be required to achieve normal glucagon secretion from the transplanted islets.
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Original Articles|
January 01 1997
Defective Glucagon Secretion During Sustained Hypoglycemia Following Successful Islet Allo- and Autotransplantation in Humans
David M Kendall;
David M Kendall
Diabetes Center and the Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Minnesota Medical School
Minneapolis, Minnesota
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Adrian U Teuscher;
Adrian U Teuscher
Diabetes Center and the Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Minnesota Medical School
Minneapolis, Minnesota
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R Paul Robertson
R Paul Robertson
Diabetes Center and the Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Minnesota Medical School
Minneapolis, Minnesota
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Address correspondence and reprint requests to Dr. David M. Kendall, The Diabetes Center, Box 101 UMHC, University of Minnesota, Minneapolis, MN 55455. E-mail: [email protected].
1
RIA, radioimmunoassay.
Diabetes 1997;46(1):23–27
Article history
Received:
January 16 1996
Revision Received:
August 29 1996
Accepted:
August 29 1996
PubMed:
8971076
Citation
David M Kendall, Adrian U Teuscher, R Paul Robertson; Defective Glucagon Secretion During Sustained Hypoglycemia Following Successful Islet Allo- and Autotransplantation in Humans. Diabetes 1 January 1997; 46 (1): 23–27. https://doi.org/10.2337/diab.46.1.23
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