Gastric Inhibitory Polypeptide (GIP) Response in Diabetes Using a Highly Specific Antiserum

Abstract

Gastric inhibitory polypeptide (GIP), a hormone secreted from the proximal small gut, is recognized as a major component of the enteroinsular axis. However, circulating levels of GIP in diabetes have been reported to be exaggerated, normal or decreased following glucose ingestion, which may be due to the presence of variable crossreacting immunoreactive GIP forms in the circulation. We have raised an antibody (S705) which recognizes only 5 kDa GIP. Using this antiserum we have measured circulating GIP levels in 18 healthy volunteers, and 13 Type 2 diabetic and 9 Type 1 diabetic patients following ingestion of 75 g glucose. As expected, blood glucose levels and blood insulin levels are significantly abnormal in the diabetic groups. On the other hand, circulating GIP levels at all time-points and integrated incremental GIP over 120 min were not different from the control group. However, we cannot exclude the possibility that apparently normal immunoreactive GIP levels in diabetes might conceal subtle alterations in biological activity which could play a role in the pathogenesis of the disease.

Secretion of Glucose-Dependent Insulinotropic Polypeptide in Patients With Type 2 Diabetes

“…1. Of the retrieved references, 22 (6,10–30) (28 datasets) fulfilled our inclusion criteria (Supplementary Table 1). Total GIP was measured by antiserum R65 in 12 of the articles, by the ELISA kit (Millipore Corporation, Billerica, MA) in 7 articles, by the radioimmunoassay kit from (RIA kit; Phoenix Laboratories, Belmont, CA) in 2 articles, and by antibody S705, which recognizes 5-kD GIP, in 1 article.…”

“…Studies (6,10–30) investigating adult patients with type 2 diabetes and appropriate healthy control subjects (weight-matched nondiabetic subjects) reporting plasma total GIP responses after oral glucose tolerance test (OGTT) or meal test were included. Data from studies that used early nonspecific assays (5,31–39) were analyzed separately and were not included in the main meta-analyses.…”

Gastric Inhibitory Polypeptide (Gip) Responses in Type 2 Diabetes Using Three Different Antibodies

“…Different investigators using different RIA systems found normo-, hypo-and hyperGIPemia in type 2 diabetes [7][8][9][10][11][12][13][14]. Using the same assay system employing three different porcine GIP antisera, we have found hypo-and normoGIPemia in type 2 diabetes.…”

“…It is well established that circulating GIP consists of three immunoreactive GIP (IR-GIP) forms displaying variable immunoreactivity with different porcine GIP antisera [18,19], In this study, the use of ethanol extract of plasma in the assay system totally removed void volume IR-GIP, resulting in elimination of the variable contribution of this IR-GIP form [18]. It has been reported that a specific GIP antiserum for 5000 IR-GIP form did not show any difference in GIP responses in diabetes compared with a normal group [12]. Although variable cross-reactivity has been displayed by 8000 IR-GIP to most GIP antisera, it has been reported that 8 kDa GIP is not insulinotropic, even in pharmacological doses [20].…”

“…As a result, considerable investigations have been performed to define the role of GIP in type 2 diabetes. Using different radioimmunoassay (RIA) systems, following oral glucose load, grossly different and conflicting data on GIP in type 2 diabetes have been published [7][8][9][10][11][12][13][14]. The present work was therefore undertaken to study GIP responses in type 2 diabetes using three different antisera in the same assay system.…”