To investigate the possibility that an abnormality of the entero-insular axis is responsible for the hyperinsulinaemia of obesity, serum immunoreactive gastric inhibitory polypeptide (IR-GIP) and insulin (IRI) were measured after the ingestion of a liquid mixed test meal, glucose or fat, in normal weight and obese subjects. The latter were divided into a group with normal oral glucose tolerance (nOGT) and a group with pathological glucose tolerance (pOGT). Fasting levels of IR-GIP were significantly elevated in the obese group with pOGT. After the mixed meal the overweight subjects showed a significantly greater response of IR-GIP than the controls, with highest levels in the pOGT group. Simultaneously, the IRI response was significantly greater in the obese subjects than in the controls. The increases of IR-GIP and IRI after an oral load of 100 g glucose were normal in the obese subjects, but showed a significantly greater integrated response in the obese patients with pOGT. The ingestion of 100 g fat induced no IRI release but a significantly greater release of IR-GIP in the obese subjects, irrespective of their glucose tolerance. It is concluded that fat is a stronger releaser of IR-GIP than glucose. The effect of a combined load of glucose (30 g) and fat (100 g) was also compared in obese and nOrmal weight subjects with the effect of either alone. Fat but not glucose released significantly more IR-GIP in obese subjects. In normal weight controls, but not in obese subjects, the IR-GIP release after fat plus glucose became significantly smaller than after fat alone. Since only the combined ingestion of glucose and fat and not fat alone releases insulin it is suggested that endoge-Fachklinik fiir Diabetes und Stoffwechselkrankheiten, Bad Lauterberg im Harz, FRG nous insulin inhibits GIP release and that this feedback control between insulin and GIP is defective in patients with obesity.
The response of serum immunoreactive gastric inhibitory polypeptide (IR-GIP), gastrin (IRG) and insulin (IRI) to a mixed standard meal was measured in 15 controls, 6 patients with coeliac disease, 26 patients with chronic pancreatitis and partial duodenopancreatectomy (Whipple's procedure). Serum levels of IR-GIP, IRG and IRI were significantly reduced in patients with coeliac disease. The serum glucose increase was significantly smaller only during the first hour after the meal. Since small intestinal GIP- and G-cells are situated mainly in the glands of duodenal and jejunal mucosa their absolute number is not significantly reduced in coeliac disease. It is suggested that the release of IR-GIP and duodenal IRG is influenced by the rate of absorption of nutrients. In patients with chronic pancreatitis the IR-GIP release is significantly greater than in controls, the IRG release normal and the IRI response delayed. After Whipple's procedure the IR-GIP response is increased significantly while the IRG secretion is abolished. This demonstrates that the duodenum is not necessary for GIP release and that pancreatic and jejunal gastrin are without clinical significance.
Thirty human insulinomas have been investigated histologically and their immunoreaetive insulin (IRI) content estimated. In most eases immunohistological and ultrastruetural studies were also performed and the percentage of proinsulin-like components (PLC) in the tumour determined. Except for 1 ease the II~I concentration in the tumours was lower (0.01-89.0 U/g) than in the islet tissue. Histologically, immunohistologically and ultrastrueturally a variable number of tumour cells contained few and often no beta-granules, indicating a decreased storage capacity for insulin. This defective storage capacity seems to be the major functional abnormality of insulinoma cells. Ultrastrueturally four types of insulinoma can be distinguished. The ultrastructural diagnosis of an insulinoma can only be made in t?~e I (typicai beta-granules, 13 cases) and type II (typieM and at~2pical granules, 7 eases) but, not in type III (atypical granules only, 4 eases) and type IV (virtually agranular, 4 eases). The type IV tumours had the lowest IRI concentration and did not respond to diazoxide treat-merit. The IRI concentration of the uninvolved pancreas of 19 patients was 2.0~0.2 U/g and in the range of nondiabetic adults.-The percentage PLC in 19 insulinomas was higher (5.3-22%) than in the pancreas of human adults with and without insulinoma (1.7-4.8%). The percentage of PLC in the serum of patients with insulinoma was always higher than in their tumours (33-61%). It is suggested that the higher PLC levels found in the tumour and serum of insulinoma patients are the consequence of the reduced storage capacity of the tumour cells resulting in a rapid passage through the granular route or even a non-granular release of newly synthesized insulin.
Summary. Gastric Inhibitory Polypeptide (GIP; 1 or 10 ~tg/ml) potentiated glucose-induced (8 or 16.6 mM) insulin (IRI) release from isolated rat pancreatic islets. Basal release was unaffected. The threshold concentration of glucose necessary for GIP to modulate IRI release was between 6 and 8 mM. GIP had no effect on IRI release from islets submitted to a maximal glucose stimulus (25 mM).
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