Ileal Effect on Blood Glucose, HbA1c, and GLP-1 in Goto-Kakizaki Rats

There have been enumerable studies on the effects of glucagon-like peptide-1 (GLP-1) on satiety and pancreatic islet function, stimulating the advocacy of surgical transposition of the ileum (rich in GLP-1-generating L-cells) higher in the gastrointestinal tract for earlier stimulation. In the Goto-Kakizaki rat with naturally occurring type 2 diabetes, we studied the influence of ileal exclusion (IE) and ileal resection (IR) on blood glucose, hemoglobin A1c (HbA1c), and GLP-1. In six control (Ctrl), 10 IE, and 10 IR rats, over 12 weeks of follow-up, we determined blood glucose, HbA1c, and GLP-1. Two animals in the IE and IR groups did not survive to week 13. Both operated groups weighed more than the Ctrl group at baseline and at 13 weeks; thus, IE and IR did not retard weight gain (p < 0.05). All three groups were equally hyperglycemic at week 13: 255 +/- 10.2 Ctrl, 262 +/- 11.0 IE, 292 +/- 17.8 IR (mg/dl +/- SEM). The three groups had statistically identical markedly elevated HbA1c percentages at week 13: 14.7 +/- 28 Ctrl, 11.7 +/- 3.4 IE, 13.8 +/- 3.5 IR (% +/- SEM). The end-study GLP-1 values (pM +/- SEM) were 5 +/- 0.9 Ctrl, 33 +/- 8.9 IE, and 25 +/- 6.7 IR. P values for intergroup differences were IE vs. Ctrl 0.02, IR vs. Ctrl 0.02, and IE vs. IR 0.59. Neither IE nor IR resulted in a decrease in the mean GLP-1 level. On the contrary, the exclusion or resection of the L-cell rich ileum raised GLP-1 levels 5- to 6-fold. This increase in the GLP-1 was not associated with the mitigation of hyperglycemia or elevated HbA1c levels.