Regulation of [alpha]-cell function by the [beta]-cell during hypoglycemia in Wistar rats: the "switch-off" hypothesis

The glucagon response is the first line of defense against hypoglycemia and is lost in insulin-dependent diabetes. The [beta]-cell "switch-off" hypothesis proposes that a sudden cessation of insulin secretion from [beta]-cells into the portal circulation of the islet during hypoglycemia is a necessary signal for the glucagon response from downstream [alpha]-cells. Although indirect evidence exists to support this hypothesis, it has not been directly tested in vivo by provision and then discontinuation of regional reinsulinization of [alpha]-cells at the time of a hypoglycemic challenge. We studied streptozotocin (STZ)-induced diabetic Wistar rats that had no glucagon response to a hypoglycemic challenge. We reestablished insulin regulation of the [alpha]-cell by regionally infusing insulin (0.025 [micro]U/min) directly into the superior pancreaticoduodenal artery (SPDa) of STZ-administered rats at an infusion rate that did not alter systemic venous glucose levels. SPDa insulin infusion was switched off simultaneously when blood glucose fell to