Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The entero-insular axis comprises direct substrate stimulation of the islet cells by the absorbed nutrients and signal transmission by endocrine factors and nerves. The extent of neural influences has not yet been evaluated. GIP is the main incretin candidate. GIP release is dependent on nutrient absorption. Therefore, GIP abnormalities occur in a large number of gastrointestinal and metabolic diseases. These secondary changes are rarely of clinical significance. GIP hypersecretion may, however, contribute to the increased lipogenesis in obesity and the hypoglycemia in the late dumping syndrome. In type II diabetes hyper- and hyposecretion of GIP has been found but no correlation between GIP and insulin response. GIP abnormalities are not identical with disturbances of the entero-insular axis. These can only be evaluated by estimating the incretin effect (comparing the insulin response to oral glucose with the insulin response to an isoglycaemic iv glucose infusion). A decreased incretin effect has been observed in patients with jejuno-ileal bypass and in type II diabetes. In neither condition was a correlation found between incretin effect and GIP response. It is concluded that disturbances of the entero-insular axis are rarely explained by GIP abnormalities. Therefore, other humoral gut factors must exist. Also the neural part of the entero-insular axis requires exploration in health and disease.
 ...
PMID:Disturbances of the entero-insular axis. 635 14

Twenty-three obese and 17 control subjects were studied after ingestion of a heavy breakfast. Blood samples were drawn before and at 30, 60, 90, 120, 150, and 180 min after the start of the meal. The m ean serum insulin level was significantly (p less than 0.02) higher in the obese than in the control group throughout the study, whereas the mean blood glucose concentration was significantly (p less than 0.02) higher in the obese group at 30, 60, and 90 min only. No significant differences between the two groups were noted in fasting or in postprandial plasma GIP, and it appears that hypersecretion of GIP is not responsible for the hyperinsulinemia seen in obesity.
 ...
PMID:GIP and insulin responses to a test meal in healthy and obese subjects. 636 17

The involvement of the gut hormone GIP (gastric inhibitory polypeptide, glucose-dependent insulinotropic polypeptide) in the hyperinsulinemia of the adult obese Zucker rat was investigated. Glucose, insulin, and GIP responses to oral glucose were compared in lean and obese rats. The sensitivity of the isolated, perfused pancreas to glucose and GIP was studied in basal and hyperglycemic conditions in lean and obese rats. Immunocytochemical studies of the gut and pancreas were also carried out. The glucose and GIP responses to oral glucose were similar in lean and obese rats, but obese animals were hyperinsulinemic compared with lean controls under fasting conditions and after oral glucose. The isolated, perfused pancreas of obese Zucker rats had an elevated insulin response to 300 mg/dl glucose. GIP increased the insulin response to 300 mg/dl glucose threefold in both lean and obese rats. At basal glucose levels (80 mg/dl), GIP augmented insulin release in obese but not in lean rats. Immunocytochemical studies demonstrated the presence of enlarged islets in obese rats due to an increase in the B-cell mass. A-, D-, and PP-cells appeared normal. Obese and lean rats had similar numbers of GIP-containing cells in the gut. This study suggests that GIP may contribute to the fasting hyperinsulinemia characteristic of adult obese Zucker rats. GIP infusion to achieve levels equivalent to those seen in the basal state are capable of stimulating insulin release in the absence of hyperglycemia in the obese rat, which suggests an impairment of the regulatory mechanisms controlling the glucose-dependent insulinotropic action of GIP in these animals.
 ...
PMID:Gastric inhibitory polypeptide (GIP) and insulin release in the obese Zucker rat. 637 59

Eight morbidly obese subjects and 12 controls were studied with an oral test meal and a heavy duodenal infusion with fat and glucose. Five of the controls were excluded because of nausea and vomiting after the duodenal stimulation whereas none of the obese subjects noted any discomfort. There was no difference in plasma GIP secretion between the two groups neither after the oral nor after the duodenal stimulation. The present study supports our previous conclusion of an unaltered GIP secretion in obesity.
 ...
PMID:Similar plasma GIP responses in obese and lean subjects after an oral test meal and after intraduodenal stimulation with fat and glucose. 639 18

Biliopancreatic bypass for obesity entails a 2/3 distal gastrectomy with Roux-en-Y reconstruction, being the small bowel transected at its midpoint and the enteroenteroanastomosis placed 50 cm proximal to the ileocecal valve. Insulin and GIP fasting and meal-stimulated plasma concentrations were determined in 13 nonobese healthy volunteers, in 13 nonoperated obese patients, in 11 subjects within two months, in 12 subjects four to twelve months, and in 7 subjects fifteen to twenty months after operation. Insulin in the obese patients was significantly higher than in the control group. Postoperatively these patients showed a sharp reduction in basal and postprandial values. Plasma insulin levels, both basally and following the test meal, were very similar in the 15-20 month and the control group. Plasma GIP fasting level, meal-stimulated peak and integrated response in the obese group were higher than in control group. Due to the extreme variability among subjects in the obese group, the difference was significant only for the mean peak response. All values were greatly reduced after surgery. The mean fasting level in the 15-20 month group was very similar to that in the control group, and both peak and integrated responses were significantly lower than in the preoperative and control groups.
 ...
PMID:[Behavior of plasma insulin and GIP in obese patients subjected to biliopancreatic bypass]. 700 41

Hypersecretion of immunoreactive gastric inhibitory polypeptide (IRGIP) has been reported previously in patients with diabetes mellitus (DM) and obesity. To ascertain the relative contribution of glucose intolerance and obesity to the abnormalities of IRGIP secretion, 114 subjects were studied during a standard oral glucose (75 g) tolerance test; responses of glucose, insulin, C-peptide, IRGIP, and glucagon were evaluated. The subjects were divided into six subgroups according to body weight and the degree of glucose intolerance. In normal weight subjects, the IRGIP response to oral glucose was significantly higher in the patients with impaired glucose tolerance (IGT) and DM than in the healthy control subjects (P less than 0.05). In the obese subjects, no significant differences in mean IRGIP responses could be detected among control, IGT, and DM subjects. In spite of similar IRGIP responses, the obese IGT patients did release more insulin than the obese control subjects, suggesting that incretin factors other than GIP may be operative in this condition. When obese and nonobese patients were compared, the obese subjects with normal glucose tolerance released a greater amount of IRGIP and insulin than the normal weight controls, whereas no significant difference between obese and nonobese could be found within the IGT and DM groups. We conclude that in the absence of obesity, glucose intolerance may induce IRGIP hypersecretion. On the other hand, obesity is associated with IRGIP hypersecretion, and glucose intolerance has no further effect, indicating a different pathogenetic mechanism for the IRGIP abnormalities. In both the obese and nonobese diabetic groups, IRGIP hypersecretion was associated with a failure of plasma glucagon levels to fall after oral glucose; this effect might be related to the glucagonotropic action of this peptide.
 ...
PMID:Gastric inhibitory polypeptide release after oral glucose: relationship to glucose intolerance, diabetes mellitus, and obesity. 704 54

Mexican Americans, a group at high risk for type II diabetes mellitus, have higher postprandial insulin and glucose levels when compared to non-Hispanic whites. A rapid rate of gastric emptying contributes to an increased rate of nutrient absorption and subsequent greater elevation of postprandial glucose and insulin levels. A more rapid rate of gastric emptying and hyperinsulinemia have been observed in patients with recently diagnosed type II diabetes mellitus. In this study, we examined whether Mexican Americans have a more rapid rate of gastric emptying than non-Hispanic whites. Gastric emptying studies were performed on 32 nondiabetic Mexican Americans and on 31 nondiabetic non-Hispanic whites. The rate of gastric emptying following a liquid glucose meal was measured. Serum insulin, plasma glucose, and GIP levels were measured in fasting and postprandial blood samples collected at 15-min intervals for 2 hr. Adjusting for age, body mass index, and gender, the gastric half-emptying time of a glucose meal was significantly (P < 0.05) more rapid for the Mexican American subjects (56.5 +/- 3.4 min) compared to the non-Hispanic white subjects (66.4 +/- 3.5 min). Nondiabetic Mexican Americans empty a liquid glucose meal more rapidly from their stomachs than nondiabetic non-Hispanic whites. Rapid gastric emptying is associated with hyperinsulinemia as a normal physiologic response to increased nutrient availability. The rapid gastric emptying observed in nondiabetic Mexican Americans is associated with hyperinsulinemia and could be a contributing factor for the increased risk of obesity and type II diabetes in this population.
 ...
PMID:Gastric emptying in Mexican Americans compared to non-Hispanic whites. 789 57

The literature with respect to GIP is flooded with conflicting data especially with respect to its role in type 2 diabetes mellitus, obesity, type 1 diabetes mellitus and chronic pancreatitis. This review describes possible reasons for the discrepancies which include species variation of GIP, heterogeneity of molecules with different immunoreactivity and bioactivity, deterioration of immunoreactivity of standard and sample on prolonged storage and the effect of the preceding intake of type and quantity of food. The problems can be resolved by raising antibodies to synthetic human GIP and its fragments, the chemical characterization of and the raising of antibodies to immunoreactive GIP 8000, the correct storage of samples and the standard preparation of subjects prior to experimental procedures.
 ...
PMID:Conflicting gastric inhibitory polypeptide data: possible causes. 847 32

A definitive assessment of the relative roles of insulin resistance and insulin deficiency in the etiology of NIDDM is hampered by several problems. 1) Due to better methodology, data on insulin resistance are generally more accurate and consistent than data on insulin deficiency. 2) In source data, case-control studies are prone to selection bias, while epidemiological associations, whether cross-sectional or longitudinal, are liable to misinterpretation. 3) Insulin secretion and action are physiologically interconnected at multiple levels, so that an initial defect in either is likely to lead with time to a deficit in the companion function. The fact that both insulin resistance and impaired insulin release have been found to precede and predict NIDDM in prospective studies may be in part a reflection of just such relatedness. 4) Direct genetic analysis is effective in rarer forms of glucose intolerance (MODY, mitochondrial mutations, etc.) but encounters serious difficulties with typical late-onset NIDDM. Despite these uncertainties, the weight of current evidence supports the view that insulin resistance is very important in the etiology of typical NIDDM for the following reasons: 1) it is found in the majority of patients with the manifest disease; 2) it is only partially reversible by any form of treatment (117); 3) it can be traced back through earlier stages of IGT and high-risk conditions; and 4) it predicts subsequent development of the disease with remarkable consistency in both prediabetic and normoglycemic states. Of conceptual importance is also the fact that the key cellular mechanisms of skeletal muscle insulin resistance (defective stimulation of glucose transport, phosphorylation, and storage into glycogen) have been confirmed in NIDDM subjects by a variety of in vivo techniques [ranging from catheter balance (118) to multiple tracer kinetics (119) to 13C nuclear magnetic resonance spectroscopy (120)], and have been detected also in normoglycemic NIDDM offspring (121). If insulin resistance is a characteristic finding in many cases of NIDDM, insulin-sensitive NIDDM does exist. On the other hand, given the tight homeostatic control of plasma glucose levels in humans, beta-cell dysfunction, relative or absolute, is a sine qua non for the development of diabetes. If insulin deficiency must be present whereas insulin resistance may be present, is this proof that the former is etiologically primary to the latter? If so, do we have convincing evidence that the primacy of insulin deficiency is genetic in nature? The answer to both questions is negative on several accounts. The defect in insulin secretion in overt NIDDM is functionally severe but anatomically modest: beta-cell mass is reduced by 20-40% in patients with long-standing NIDDM (122). Moreover, the insulin secretory deficit is progressively worse with more severe hyperglycemia (123) and recovers considerably upon improving glycemic control (124). These observations indicate that part of the insulin deficiency is acquired (through glucose toxicity, lipotoxicity, or both). In addition, although insulin deficiency is necessary for diabetes, it may not always be sufficient to cause NIDDM. In fact, subtle defects in the beta-cell response to glucose may be widespread in the population (108, 125) and only cause frank hyperglycemia when obesity/insulin resistance stress the secretory machinery. Conceivably, there could be beta-cell dysfunction without NIDDM just as there is insulin resistance without diabetes. Incidentally, any defect in insulin secretion, whether in normoglycemic or hyperglycemic persons, could be due to other factors than primary beta-cell dysfunction: amyloid deposits in the pancreas (126), changes in insulin secretagogues (amylin, GLP-1, GIP, galanin) (127-130), early intrauterine malnutrition (131). Finally, the predictive power of early changes in insulin secretion for the development of typical NIDDM is generally lower than that of insulin
 ...
PMID:Insulin resistance versus insulin deficiency in non-insulin-dependent diabetes mellitus: problems and prospects. 971 76

Findings on the effects of GIP indicate that its incretory effect on stimulation of insulin secretion under conditions of hyperglycaemia is more important than the formerly known effect of enterogastrone. Numerous experimental trials provide evidence that GIP can participate in the regulation of the postprandial glucose and lipid metabolism and circulation in the splancnic area. The physiological action of GIP has however still obscure consequences in pathological conditions. Because GIP secretion by the mucosa of the small intestine is conditioned by nutrient absorption and its incretory effect on the functional capacity of the B-cells of the pancreas, it is assumed that it is of clinical importance in diseases of the digestive tract and in metabolic disorders. The author presents a review of recent findings on GIP and its action in diabetes, obesity, chronic pancreatic disease and other pathological conditions. In view of the controversial reports the clinical importance of GIP is not quite clear so far.
 ...
PMID:[Clinical significance of glucose-dependent insulinotropic polypeptide (GIP)]. 982 Jan 11


<< Previous 1 2 3 4 5 6 7 8 9 Next >>