Intact Glucagon-like Peptide-1 Levels are not Decreased in Japanese Patients with Type 2 Diabetes

Abstract

Abstract. Impaired secretion of glucagon-like peptide 1 (GLP-1) has been suggested to contribute to the deficient incretin effect in patients with type 2 diabetes mellitus (t2Dm). Recent studies, however, have not always supported this notion. Since Japanese patients with t2Dm usually have severe impairment in the early-phase of insulin secretion, the measurement of incretin secretions in Japanese t2Dm patients would be useful for assessing the association between incretin levels and insulin secretion. We conducted an oral glucose tolerance test (75 g) (oGtt) and meal tolerance test (480 kcal) (mtt) for subjects with normal glucose tolerance (NGt, n=12), subjects with impaired glucose tolerance (iGt, n=7), and t2Dm patients (n=21). the tests were carried out over 120-min study periods on separate occasions. intact GLP-1, GiP, and dipeptidyl peptidase (DPP)-iV were measured by eLiSa. t2Dm exhibited an impaired early phase of insulin secretion and a reduction in glucagon suppression. There were no significant differences in GLP-1 or GIP levels at each sampling time among NGt, iGt, and t2Dm after the ingestions; hence the incremental areas under the curve (iauc) for the three groups were quite similar. the levels of DPP-iV, a limiting enzyme for the degradation of incretins, were comparable among the three groups. the GLP-1-iauc was not correlated with iaucs of insulin, c-peptide, or glucagon determined by the oGtt or the mtt. We concluded that intact GLP-1 levels are comparable between non-diabetics and t2Dm, suggesting that impaired insulin secretion in Japanese t2Dm is not attributable to defect in GLP-1 secretion.

Preserved GLP-1 and exaggerated GIP secretion in type 2 diabetes and relationships with triglycerides and ALT

“…Another explanation for the higher GLP-1 response after oral glucose vs the solid mixed meal would be an accelerated gastric emptying that has been described for early diabetic patients during a liquid meal (38,39). In line with earlier studies, GLP-1 response among persons with IH was unaltered (7,8,10,40,41). This suggests that a defect in GLP-1 secretion is unlikely to precede type 2 diabetes development, which is consistent with earlier findings among first-degree diabetes relatives, and in induced insulin resistance among healthy subjects (27,42).…”

“…Earlier studies among diabetic patients mostly report no change in GIP response after a meal or oral glucose (10,11,12,13), a higher response (7, 9, 41) or a slightly lower response (8,44). Similarly, GIP response among persons with IH has been reported unaltered (8,41), decreased (40) or increased (7).…”

“…Studies that directly compared GLP-1 responses following oral glucose vs mixed meal are scarce and the available studies did not find an altered GLP-1 response after both interventions among diabetic patients (7). GIP responses were found to be reduced (8), increased (7,9), but mostly unchanged in patients with diabetes (10,11,12,13). Possible explanations for these inconclusive findings on incretin responses among diabetic patients may relate to the assay used, the test meal, participant characteristics and probably sample size.…”

Incretin secretion and serum DPP-IV activity in Korean patients with type 2 diabetes

“…Type 2 diabetic patients have a marked reduction in incretin effects [1], although it remains unclear whether deficiencies in GLP-1 secretion contribute to these reduced incretin effects [2][3][4][5][6][7][8][9]. Most studies have focused on Western type 2 diabetic patients.…”

Glucagon-like Peptide-1 Suppresses the Proliferation and Migration of Vascular Smooth Muscle Cells: Implications for Preventive Effects on Atherosclerosis

“…The concentrations of GLP-1 used in vitro 0.1−1 nmol / l in studies of human VSMC proliferation and migration are higher than concentrations found in vivo in plasma from nonfasted patients with diabetes 2−40 pmol / l 24,25 . It has been reported that GLP-1 administered via buccal tablets 119 nmol or via continuous infusion 2.16 nmol / kg per day for 2 days increases plasma GLP-1 concentrations in humans to a peak of 100−120 pmol / l 26,27 .…”