Impaired glucose-induced glucagon suppression after partial ...

A number of previous studies in rats and mice have suggested that functional alterations in
islet secretion are only detectable after reductions in beta-cell mass in the range of ~80-90%
(44, 45), whereas less extensive pancreatic resections can be tolerated without measurable
disturbances in circulating islet hormone concentrations (46). These reports are contrasted by
larger animal studies, where alterations in both insulin and glucagon secretion occurred
already after an ~50% beta-cell loss (15, 17, 47). Furthermore, studies in individuals with
impaired fasting glucose, who typically already exhibit defects in insulin secretion (48), have
revealed an ~50% deficit in beta-cell mass even before the full onset of type 2 diabetes (49).
The present studies showing marked alterations in both insulin and glucagon secretion after
hemipancreatectomy are therefore consistent with these previous studies and re-emphasize the
importance of beta-cell mass for the maintenance of glucose homoeostasis.
There has been some debate regarding the distribution of islet alpha- and beta-cells within
the pancreas. Indeed, in different studies in humans and in animal models, the majority of
alpha- and beta-cells were found in the pancreatic tail, whereas Pancreatic Polypeptide
secreting cells were predominantly shown in the pancreatic head and the uncinate process (50-
54). In the present studies fasting glucagon concentrations were almost unchanged after
pancreatic head resection, but substantially lowered after removal of the pancreatic tail. This
may suggest a predominance of alpha-cells in the pancreatic tail compared to the head and
body regions. However, since the maximum glucagon responses have not been tested directly,
this study does not allow for valid conclusions in this regard.
The present and our previous study (18) have also shown significant improvements in
glycaemia within the first 90 min after the oral glucose load, which is surprising in light of the
concomitant reduction in insulin secretion. This may on the one hand be due to an
improvement insulin sensitivity induced by the removal of the abnormal pancreatic tissue. On
the other hand it seems possible that the transient reduction in glycaemia immediately after
glucose ingestion was caused by a delay in gastric emptying secondary to the surgical trauma.
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