Glucose Potentiation Of Arginine-induced Insulin Secretion Research Articles

Acute Insulin Responses to Glucose and Arginine as Predictors of β-Cell Secretory Capacity in Human Islet Transplantation

Islet transplantation for type 1 diabetes can enable the achievement of near-normal glycemic control without severe hypoglycemic episodes. How much an islet (beta-cell) graft may be contributing to glycemic control can be quantified by stimulatory tests of insulin (or C-peptide) secretion. Glucose-potentiation of arginine-induced insulin secretion provides a measure of functional beta-cell mass, the beta-cell secretory capacity, as either AIR(pot) or AIR(max), but requires conduct of a hyperglycemic clamp. We sought to determine whether acute insulin responses to intravenous glucose (AIR(glu)) or arginine (AIR(arg)) could predict beta-cell secretory capacity in islet recipients. AIR(arg) was a better predictor of both AIR(pot) and AIR(max) (n=10, r2=0.98, P<0.0001 and n=7, r2=0.97, P<0.0001) than was AIR(glu) (n=9, r2=0.78, P=0.002 and n=6, r2=0.76, P=0.02). Also, the measures of beta-cell secretory capacity were highly correlated (n=7, r2=0.98, P<0.0001). These results support the use of AIR(arg) as a surrogate indicator of beta-cell secretory capacity in islet transplantation.

A Report of the Vancouver Forum on the Care of the Live Organ Donor: Lung, Liver, Pancreas, and Intestine Data and Medical Guidelines

An international conference of transplant physicians, surgeons, and allied health professionals was held in Vancouver, Canada, on September 15 and 16, 2005 to address the care of the live lung, liver, pancreas, and intestine organ donor. The Vancouver Forum was convened under the auspices of the Ethics Committee of The Transplantation Society. Forum participants included over 100 leaders in organ transplantation, representing many countries from around the world, including participants from the following continents: Africa, Asia, Australia, Europe, North and South America. The objective of the Vancouver Forum was to develop an international standard of care for the live lung, liver, pancreas and intestinal organ donor. This Vancouver Forum followed a conference convened in Amsterdam on the care of the live kidney donor (1, 2). There were four organ specific work groups at the Vancouver Forum: lung, liver, pancreas and intestine. Each organ work group addressed the following topics in concert and reported their findings in a plenary presentation to all participants:

AIRarg and AIRgluc as predictors of insulin secretory reserve

Various brief metabolic tests have been proposed as surrogate measures of insulin secretory reserve, which is normally determined by the more complicated and labor-intensive method of glucose potentiation of arginine-induced insulin secretion (GPAIS). This article provides correlations between insulin responses to intravenous arginine (AIRarg) and intravenous glucose (AIRgluc) in 39 normal control subjects in whom insulin secretory reserve was measured by GPAIS. The correlation coefficients were .78 and .77, respectively, both of which were highly statistically significant ( P < .001). These results indicate that either AIRarg or AIRgluc, tests that can be performed in less than 15 minutes, can be used as reliable predictors of insulin secretory reserve in normal controls and, presumably, in recipients of islet and pancreas transplantation.

Consequences on beta-cell function and reserve after long-term pancreas transplantation.

beta-Cell replacement in diabetes using pancreatic islets or beta-cell surrogates is a research area undergoing intense scrutiny. Once this approach is demonstrated to be reproducibly successful, the next major issue will be the length of time that success will be sustained. Whole and segmental pancreas transplants are now successful for up to two decades. Study of these grafts can provide insight into and predictions about beta-cell function and reserve when islet transplantation becomes a routine. The studies described herein investigated 102 human whole and segmental transplant recipients and control subjects to address the following five questions. 1) Is the usual reciprocal relationship between the acute insulin response to intravenous glucose (AIR(gluc)) and the level of fasting plasma glucose (FPG) maintained in pancreas transplant recipients? 2) Do recipients who have no AIR(gluc) have an acute insulin response to intravenous arginine (AIR(arg))? 3) Do recipients of whole pancreata from cadaveric donors have twice the amount of insulin secretory reserve as that found in recipients of 50% segmental grafts from living, related donors? 4) What clinically accessible measure of insulin secretion best correlates with glucose potentiation of arginine-induced insulin secretion (GPAIS)? 5) Do successful pancreas transplant recipients evince time-dependent declines in beta-cell function and glycemic regulation when studied long term and longitudinally? The results demonstrate that 1) the normal relationship between AIR(gluc) and fasting glucose levels is maintained despite systemic venous drainage of allografts and consequent hyperinsulinemia; 2) AIR(gluc) and AIR(arg) decrease in parallel as fasting glucose levels rise, although AIR(arg) is still present after AIR(gluc) disappears; 3) AIR(arg) and AIR(gluc) are strongly predictive of beta-cell mass; 4) AIR(arg) and AIR(gluc) are strongly predictive of insulin secretory reserve; and 5) transplant recipients who have successfully maintained normoglycemia for an average of 10 years and up to 22 years nonetheless experience time-related declines in beta-cell function.