Effect of hemipancreatectomy and of pancreatic diversion on the tolerance to a glucose load in humans

Background The role of the pattern, quantity and site of insulin secretion in the tolerance to a glucose challenge is not fully evaluated in humans be cause it is difficult to obtain appropriate clinical models. Design To address this issue, we studied subjects with reduced pancreatic m ass (hemipancreatectomized, HEMI), systemic insulin delivery (pancreas tran splant recipients, PTX), and two control groups (healthy, CON; and with uve itis on the same immunosuppression as PTX, UVE), with an hyperglycaemic cla mp (study 1, + 4.2 mmol L-1), using a repeat experiment (study 2) with a fi xed glucose infusion, calculated to increase by 35% that in study 1. Results In study 1, CON increased glucose uptake to 20 +/- 3 mu mol kg(-1) min(-1) after a biphasic insulin response. In study 2, CON further increase d the glucose uptake via an increment in prehepatic insulin secretion that stimulated insulin sensitivity without changes in peripheral insulin and gl ucose concentrations. HEMI and PTX had 35% less glucose uptake in study 1, compared to CON, and increased glucose concentrations (+ 1.6 mmol L-1) in s tudy 2. UVE had an intermediate defect. The causes of intolerance were diff erent: HEMI had a defective first-phase insulin secretion (50% peripheral i nsulin concentrations) but maintained insulin sensitivity; PTX had normal p eripheral insulin but only one-third of the insulin sensitivity of CON. Conclusions Hemipancreatectomy and systemic insulin delivery impair first-p hase insulin secretion; second-phase peripheral insulinization (HEMI); insu lin sensitivity (PTX); and a mechanism evidentiated in study 2 of CON that increases insulin sensitivity in response to prehepatic insulin secretion ( both groups). Failure of these mechanisms is largely compensated by hypergl ycaemia.