Immunoreactive gastric inhibitory polypeptide and K cell hyperplasia in obese hyperglycaemic (ob/ob) mice fed high fat and high carbohydrate cafeteria diets

Abstract

The effect of diet composition on plasma and intestinal concentrations of immunoreactive gastric inhibitory polypeptide (GIP) and intestinal K cell density was examined in obese hyperglycaemic (ob/ob) mice. The mice were reared from 3 to 11 weeks of age on either stock diet, a high fat (HF) cafeteria diet or a high carbohydrate (HC) cafeteria diet. The HF cafeteria diet increased the concentration of GIP in plasma (75%) and in the intestine (118%) and increased the density (54%) of GIP-secreting K cells in the upper jejunum compared with the stock diet. Plasma and intestinal GIP concentrations were not significantly altered by the HC cafeteria diet, although the density of K cells in the upper jejunum was increased (45%). The extent of hyperglycaemia and hyperinsulinaemia in ob/ob mice was not significantly altered by the HF and HC cafeteria diets. The results indicate that an increased amount of dietary fat chronically stimulates the production and secretion of GIP, and enhances intestinal K cell density in ob/ob mice.Obese hyperglycaemic (ob/ob) mice exhibit a par¬ ticularly severe obesity and hyperinsulinaemia, marked hyperphagia and moderate hyperglycae¬ mia (Bray & York 1979; Bailey et al. 1982). Recent studies have identified excessive concentrations of immunoreactive gastric inhibitory polypeptide (GIP) in the small intestine and plasma of these mice (Flau et al. 1983, 1984a) associated with hyperplasia and increased hormone content of the intestinal GIP-secreting cells (Polak et al. 1975). Considerable evidence has implicated GIP as a physiological component of the enteroinsular axis (Brown 1982;Creutzfeldt et al. 1983), and hypersécrétion of GIP has been suggested as a factor contributing to the hyperinsulinaemia of ob/ob mice (Flatt et al. 1984a,b). The raised GIP concentrations of ob/ob mice render this mutant a convenient model for studies of GIP physiology. As noted in other species (Brown 1982), orally administered fat elicits a greater acute plasma GIP response than other nutrients in ob/ob mice (Flatt et al. 1984a), but the long-term effects of different dietary components on plasma and intestinal GIP remain to be established.The present study examines the chronic effects of excess fat and excess carbohydrate on the de¬ velopment of raised GIP concentrations in young ob/ob mice fed for 8 weeks on high fat and high carbohydrate cafeteria diets. Materials and Methods AnimalsObese hyperglycaemic (ob/ob) mice and lean (+/+) mice on the Aston background were housed as previ¬ ously (Flatt et al. 1984a). The origin and characteristics of these mice have been described elsewhere (Flatt & Bailey 1981;Bailey et al. 1982). DietsGroups of mice were fed either stock diet (Mouse breeding diet,

Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

“…This diabetic animal model is closely aligned to diabetic obesity found increasingly in humans consuming high-fat and energy-rich diets (McClean et al, 2007). The high-fat diet resulted in glucose intolerance and impaired insulin sensitivity in animals used in this study (Bailey et al, 1986;Flatt et al, 1990). Results in Fig.…”

High-fat feeding stimulates endocrine, glucose-dependent insulinotropic polypeptide (GIP)-expressing cell hyperplasia in the duodenum of Wistar rats

“…However, the bridge between high-fat obesitogenic diet and obesity comorbidities is not fully understood. High-fat feeding, such as that used in the present study, allows intestinal K-cell hyperplasia, enhancing GIP gene expression together with intestinal GIP content, ultimately resulting in high basal and feedinginduced circulating levels of GIP [6][7][8][9]. The role played by GIP in mediating the effects of HFD, i.e.…”

“…High-fat feeding induces K cell hyperplasia and glucosedependent insulinotropic polypeptide (GIP) secretion [6][7][8][9] with insulin secretion potentiating effects [10]. Blockade of GIP action by administration of a specific GIP receptor antagonist, (Pro 3 )GIP, reverses the glucose intolerance induced by HFD [11] without affecting circulating insulin concentration.…”

Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro3)GIP prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice

“…More recently it has been shown that obese diabetic (ob/ob) mice have intestinal K cell hyperplasia, markedly elevated concentrations of intestinal (2.8-fold increase) and circulating GIP (15.1-fold increase) [29,40,41] and display a diminished insulinotropic response to native GIP [11]. Additionally, ob/ob mice genetically manipulated to knock out GIP receptor function displayed significant amelioration of adiposity [30].…”