Insulin and Glucagon Secretion After Pancreatectomies Correlation of Secretion and Hormonal Contents of Remaining Pancreas

Abstract

We studied whether insulin and glucagon secretory capacities change in relation to the corresponding hormonal contents in the pancreas remnant after pancreas resection. The following groups of dogs were used: sham operated (S-O), left pancreatectomized (L-Px), right pancreatectomized (R-Px), subtotal pancreatectomized (St-Px), and total pancreatectomized (T-Px). Endocrine functions were assessed by intravenous glucose tolerance test (IVGTT) and insulin tolerance test (ITT) in each dog under anesthesia before surgery and 1 wk after. In these five groups, the insulin secretory capacities, assessed as the integrated incremental secretion of immunoreactive insulin (sigma delta IRI) from the IVGTT, decreased to 95 +/- 11, 78 +/- 9, 48 +/- 8, 12 +/- 8, and -4 +/- 4% of the respective preoperative values, and these values were proportional to the percentage residual weight (100, 64 +/- 2, 35 +/- 2, 13 +/- 2, 0%) and IRI content (100, 59 +/- 4, 45 +/- 3, 10 +/- 2, 0%) of the pancreas remnant. After surgery, glucagon secretory capacity, the integrated incremental secretion of immunoreactive glucagon (sigma delta IRG) during the ITT, decreased significantly in the L-Px, St-Px, and T-Px groups but not in the R-Px group. The sigma delta IRG values as percentages of the preoperative values were 109 +/- 25, 46 +/- 11, 89 +/- 13, 19 +/- 11, and 3 +/- 3%, respectively, for the five groups. These values were proportional to the percentage residual IRG contents of the pancreas remnants (100, 48 +/- 6, 65 +/- 8, 12 +/- 2, 0%) rather than to the percentage residual pancreatic weights.(ABSTRACT TRUNCATED AT 250 WORDS)

Deterioration of Islet β-Cell Function After Hemipancreatectomy in Dogs

“…In the ventral lobe remnant there was a significant decrease in insulin content compared with fresh ventral lobes, although the change in glucagon content was not significant. The difference in insulin and glucagon content between the normal dorsal and ventral lobes are similar to those noted in other reports (4)(5)(6)9).…”

“…In the ventral remnant, the total amount of insulin reflects the small portion of dorsal lobe tissue remaining around the pancreatic ducts. The difference in content between normal dorsal and ventral lobe (180 ± 14 vs. 154 ± 15 |xg/g, respectively) was not statistically significant, suggesting a nearly even distribution of 0-cells across the pancreas similar to other reports from both human and dog studies (5,6,9). After 12 mo, there was no decrease in insulin content in the dorsal remnant, but there was a significant decrease of insulin content in the ventral lobe, suggesting a continual loss of (3-cells or ineffective insulin storage.…”

“…An increase in perfusate glucose from 5 to 11 mM resulted in an increase in glucose-stimulated insulin secretion that could be sustained for >60 min from the normal isolated dorsal lobe. In contrast, the normal isolated ventral lobe demonstrated a reduced level of glucose-stimulated insulin secretion that could not be sustained at maximum levels beyond 20-30 min, despite the continued presence of 11 mM glucose (7,9). After 12 mo, the ability of the dorsal lobe remnant to respond to an increase in glucose concentrations from 5 to 11 mM was severely impaired compared with normal freshly isolated dorsal lobes.…”

“…Islet cellular composition differs between regions of the pancreas (4)(5)(6), and it has been suggested from in vitro studies that the dorsal lobe may have a greater response to glucose than the ventral lobe (2,4,(8)(9)(10). It is uncertain whether the reported deterioration of glucose tolerance and the possible development of diabetes may be inherent as a result of insufficient p-cell mass from half a pancreas in both the recipient and donor, or whether the donor is placed at greater risk because of the presence of the ventral pancreatic remnant (1).…”

Markedly Reduced β-Cell Function Does Not Result in Insulin Resistance in Islet Autografted Dogs

“…In vivo insulin secretion has historically been measured with a variety of secretagogues, including glucose (19)(20)(21) and arginine (22)(23)(24), and the relative merits of these secretory agents have been debated in the literature (25,26). More recently, Ward et al (27,28) and McCulloch et al (14) have proposed the slope of the glycemic potentiation (SP) of the acute insulin response to arginine (AIFy as a more sensitive measure of p-cell function than is the acute insulin response to glucose (AIR g ).…”