Diabetes, Vol 46, Issue 1 23-27, Copyright © 1997 by American Diabetes Association

ARTICLES

Defective glucagon secretion during sustained hypoglycemia following successful islet allo- and autotransplantation in humans

DM Kendall, AU Teuscher and RP Robertson
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA. kendall@lenti.med.umn.edu

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 alpha-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 insulin-independent and normoglycemic (HbA(1c), 5.8 +/- 0.2%). Neither allograft recipient required exogenous insulin and maintained HbA(1c) 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.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Zhou, T. Zhang, M. Bogdani, E. Oseid, S. Parazzoli, M.-C. Vantyghem, J. Harmon, M. Slucca, and R. P. Robertson Intrahepatic Glucose Flux as a Mechanism for Defective Intrahepatic Islet {alpha}-Cell Response to Hypoglycemia Diabetes, June 1, 2008; 57(6): 1567 - 1574. [Abstract] [Full Text] [PDF]

				S. Illouz, M. Webb, C. Pollard, P. Musto, K. O'Reilly, D. Berry, and A. Dennison Islet Autotransplantation Restores Normal Glucose Tolerance in a Patient With Chronic Pancreatitis Diabetes Care, December 1, 2007; 30(12): e130 - e130. [Full Text] [PDF]

				J. Gromada, I. Franklin, and C. B. Wollheim {alpha}-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains Endocr. Rev., February 1, 2007; 28(1): 84 - 116. [Abstract] [Full Text] [PDF]

				M. R. Rickels, M. H. Schutta, R. Mueller, J. F. Markmann, C. F. Barker, A. Naji, and K. L. Teff Islet Cell Hormonal Responses to Hypoglycemia After Human Islet Transplantation for Type 1 Diabetes Diabetes, November 1, 2005; 54(11): 3205 - 3211. [Abstract] [Full Text] [PDF]

				J. L. Larsen Pancreas Transplantation: Indications and Consequences Endocr. Rev., December 1, 2004; 25(6): 919 - 946. [Abstract] [Full Text] [PDF]

				R. P. Robertson Islet Transplantation as a Treatment for Diabetes -- A Work in Progress N. Engl. J. Med., February 12, 2004; 350(7): 694 - 705. [Full Text] [PDF]

				A. Omer, V. F. Duvivier-Kali, W. Aschenbach, V. Tchipashvili, L. J. Goodyear, and G. C. Weir Exercise Induces Hypoglycemia in Rats With Islet Transplantation Diabetes, February 1, 2004; 53(2): 360 - 365. [Abstract] [Full Text]

				R. P. Robertson Intrahepatically Transplanted Islets--Strangers in a Strange Land J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5416 - 5417. [Full Text] [PDF]

				C. Semakula, S. Pambuccian, R. Gruessner, D. Kendall, G. Pittenger, A. Vinik, and E. R. Seaquist Hypoglycemia after Pancreas Transplantation: Association with Allograft Nesidiodysplasia and Expression of Islet Neogenesis-Associated Peptide J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3548 - 3554. [Abstract] [Full Text] [PDF]

				R. P. Robertson Successful Islet Transplantation for Patients with Diabetes -- Fact or Fantasy? N. Engl. J. Med., July 27, 2000; 343(4): 289 - 290. [Full Text]