Effects of hemipancreatectomy on pancreatic alpha and beta cell function in healthy human donors.

Abstract

To assess the metabolic consequences of hemipancreatectomy in humans, we determined pancreatic beta and alpha cell function in healthy donors. Donors examined cross-sectionally were found to have significantly decreased glucose-induced phasic insulin secretion and arginine-induced insulin and glucagon secretion as compared to age, sex, and body index-matched controls. However, their fasting glucose and insulin values were not different from controls. Similar observations were found in the prospective evaluation of eight donors before and 15±2 mo after hemipancreatectomy. Beta cell reserve, as measured by glucose potentiation of arginine-induced insulin secretion, was significantly decreased in donors (maximal acute insulin response [AIR..]: donors = 666±84 pM vs controls = 1,772±234 pM) while the PG5, (the glucose value at which the half-maximal response was observed) was the same in the two groups. Donors and controls responded to 60-min continuous intravenous infusions of glucose by reaching identical serum glucose values, despite significantly lower insulin secretory responses in donors. We conclude that hemipancreatectomy in human donors is associated with decreased pancreatic alpha and beta cell function. Since donors generally maintain normoglycemia after hemipancreatectomy despite diminished insulin secretion, our data suggest that healthy humans may compensate for hemipancreatectomy by increasing glucose disposal. (J. Clin. Invest. 1992. 89:1761-1766

β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes

“…Although rodents tolerate a partial pancreatectomy in which up to 80% of the ␤-cell mass is removed (28), primates (29) and pigs (30) develop diabetes with a decrease of ␤-cell mass of ϳ50% or greater. Furthermore, humans who have had ϳ50% of their pancreas removed have abnormal glucose tolerance (some developing diabetes by more recent classification) and diminished insulin secretion in response to a hyperglycemic clamp (31)(32)(33). Taken together, these findings imply that the ϳ60% deficit in ␤-cell mass observed in the present study, particularly in the context of insulin resistance encountered in type 2 diabetes, is sufficient to play an important role in causing hyperglycemia.…”

Decrease in β-Cell Mass Leads to Impaired Pulsatile Insulin Secretion, Reduced Postprandial Hepatic Insulin Clearance, and Relative Hyperglucagonemia in the Minipig

“…Despite these differences, the reported decline of insulin pulse amplitude with no change in pulse frequency observed in the baboons after streptozocin administration is consistent with the decrease in pulse mass (and amplitude) and unchanged pulse frequency evident in the current porcine model. One year after hemipancreatectomy, humans have impaired glucose tolerance (28) and decreased first-phase insulin release (29). However, no information is available concerning pulsatile insulin release in these patients.…”

Insulin expressed from endogenously active glucose-responsive EGR1 promoter in bone marrow mesenchymal stromal cells as diabetes therapy

“…22,47 Notwithstanding the fact that only about half of normal insulin secretion was reconstituted in our study, this level of insulin restoration is clinically meaningful as life-threatening diabetic ketoacidosis is prevented in type I diabetics with merely 10% of physiological circulating insulin. 48 However, it is evident that improvements in reconstituting insulin secretion beyond what we have achieved in this study are needed for a more robust therapeutic effect. This may be achieved by optimizing cell isolation and/or culture protocols that yield therapeutically sufficient cells, gene transfer techniques that yield a larger number of transgene-expressing cells and conditions that enhance cell engraftment.…”