Deterioration of Islet β-Cell Function After Hemipancreatectomy in Dogs

Abstract

The metabolic consequences of hemipancreatectomy in living pancreas donors were tested in a dog model in which a 50% lobe-specific pancreatectomy was performed. Removal of the dorsal lobe (analogous to a donor, n = 4) resulted in a progressive increase in fasting glucose during 12 mo from 5.32 +/- 0.16 to 8.17 +/- 0.28 mM and a decrease in fasting insulin from 54 +/- 3 to 6.0 +/- 2.4 pM and glucose clearance (Kg) from 3.00 +/- 0.22 to 1.00 +/- 0.06 mM. Removal of the ventral lobe (analogous to a recipient, n = 5) did not result in a change in fasting glucose or Kg during 12 mo, although fasting insulin was reduced from 36.0 +/- 1.8 to 18.00 +/- 1.93 pM. In vitro perfusion of the remnants after 1 yr showed a deterioration in glucose-stimulated insulin secretion (5-11 mM) by the dorsal remnant (18 +/- 11 vs., 232 +/- 37%) and the ventral remnant (2.6 +/- 19 vs. 87 +/- 13%). The dorsal remnant had a higher response than the ventral remnant (46 +/- 23 vs. -16 +/- 10%, respectively) to severe hyperglucosuria (11-27.7 mM). Insulin content was unchanged in the dorsal remnant (224 +/- 16 vs. 180 +/- 14 micrograms/g), but was reduced in the ventral remnant (65 +/- 14 vs. 154 +/- 15 micrograms/g). In vitro insulin pulse intervals were reduced in both remnants (5.3 +/- 0.2 min vs. control 7.00 +/- 0.18 min). Because of the above effects on the donor when the dorsal lobe is removed, the continued use of hemipancreatectomy as a source of transplantable tissue must be questioned.

Mechanisms of Impaired Fasting Glucose and Glucose Intolerance Induced by a ∼50% Pancreatectomy

“…Presumably, there was only limited overall pancreas regeneration during the ϳ6 weeks between partial pancreatectomy and euthanasia in the current studies because the surgeon's estimate of the extent of pancreatic resection and the measured mass of pancreas remnant at euthanasia corresponded closely. Moreover, previous studies in dogs maintained for 12 months after ϳ50% pancreatectomy showed progressive hyperglycemia developing into diabetes (11). The current studies were not designed to examine ␤-cell regeneration but were focused on the impact of an acute decrement in ␤-cell mass on insulin secretion.…”

Infant nutrition and subsequent risk of Type 2 (non-insulin-dependent) diabetes mellitus

“…believe that our hypothesis cannot explain the "specific lesion" of loss of first phase insulin secretion. We find nothing particularly specific in this change since it is also seen prior to the onset of Type 1 (insulindependent) diabetes [13] and after partial pancreatectomy [14,15].…”