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1.
E. Heinze J. Schlickenrieder R. W. Holl R. Ebert 《European journal of pediatrics》1991,150(5):339-342
There is a well documented increase in the incidence of abnormal glucose tolerance in patients with Turner syndrome. To elucidate the pathophysiology of this phenomenon, we studied the serum concentrations of gastric inhibitory polypeptide (GIP) — as probably the most important hormonal factor of the entero-insular axis — in relation to impaired glucose tolerance in this syndrome. Oral glucose tolerance tests were performed in 12 Turner patients with simultaneous determination of plasma glucose, insulin and GIP. An impaired glucose tolerance (iGT) was found in four patients with a chronological age between 12.3 and 14.9 years. These patients were compared with found Turner patients of similar age and weight and a normal glucose tolerance (nGT). The highest insulin level occurred 90 min after stimulation in the patients with iGT compared to 30 min in the nGT group. Interestingly, the total areas under the insulin curves were not different. Stimulated plasma GIP concentrations and the areas under the GIP curves wer significantly lower in iGT compared to nGT patients. A disturbed entero-insular axis might contribute to the delayed — rather than diminished — release of insulin in patients with Turner syndrome and impaired glucose tolerance.Deceased February 21, 1987 相似文献
2.
The prevalence of obesity continues to grow rapidly worldwide, posing many public health challenges of the 21st century. Obese subjects are at major risk for serious diet-related noncommunicable diseases, including type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease. Understanding the mechanisms underlying obesity pathogenesis is needed for the development of effective treatment strategies. Dysregulation of incretin secretion and actions has been observed in obesity and related metabolic disorders; therefore, incretin-based therapies have been developed to provide new therapeutic options. Incretin mimetics present glucose-lowering properties, together with a reduction of appetite and food intake, resulting in weight loss. In this review, we describe the physiology of two known incretins—glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and their role in obesity and related cardiometabolic disorders. We also focus on the available and incoming incretin-based medications that can be used in the treatment of the above-mentioned conditions. 相似文献
3.
The gastrointestinal tract can assess the nutrient composition of ingested food. The nutrient-sensing mechanisms in specialised epithelial cells lining the gastrointestinal tract, the enteroendocrine cells, trigger the release of gut hormones that provide important local and central feedback signals to regulate nutrient utilisation and feeding behaviour. The evidence for nutrient-stimulated secretion of two of the most studied gut hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), along with the known cellular mechanisms in enteroendocrine cells recruited by nutrients, will be the focus of this review. The mechanisms involved range from electrogenic transporters, ion channel modulation and nutrient-activated G-protein coupled receptors that converge on the release machinery controlling hormone secretion. Elucidation of these mechanisms will provide much needed insight into postprandial physiology and identify tractable dietary approaches to potentially manage nutrition and satiety by altering the secreted gut hormone profile. 相似文献
4.
Steven N.Austad Scott Ballinger Thomas W.Buford Christy S.Carter Daniel L.Smith Jr Victor Darley-Usmar Jianhua Zhang 《药学学报(英文版)》2022,12(2):511-531
Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts. 相似文献
5.
《Scandinavian journal of gastroenterology》2013,48(8):1115-1119
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 mean serum insulin level was significantly (p < 0.02) higher in the obese than in the control group throughout the study, whereas the mean blood glucose concentration was significantly (p < 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. 相似文献
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7.
Tatsuya Kondo Sayaka Kitano Nobukazu Miyakawa Takuro Watanabe Rieko Goto Miki Sato Satoko Hanatani Masaji Sakaguchi Motoyuki Igata Junji Kawashima Hiroyuki Motoshima Takeshi Matsumura Eiichi Araki 《Internal medicine (Tokyo, Japan)》2021,60(9):1433
The gastrointestinal tract is considered an important endocrine organ for controlling glucose homeostasis via the production of incretins. A 21-year-old man emergently underwent total colectomy due to severe ulcerative colitis, and overt diabetes became evident. Weekly administration of a glucagon-like peptide (GLP)-1 receptor agonist (RA) dramatically improved his glucose control. Levels of GLP-1 or gastric inhibitory polypeptide (GIP) were low at the baseline in the duodenum and serum of the patient. After 11 months of GLP-1RA treatment, his HbA1c worsened again, and intensive insulin therapy was necessary to control his glucose levels. Our report may explain the significance of residual incretin for maintaining the pancreatic β-cell function. 相似文献
8.
Summary The response of Gastric Inhibitory Polypeptide (GIP) and insulin to a 50 g oral glucose tolerance test (OGTT) and an intravenous glucose infusion (IVGI), which copied the changes in plasma glucose concentrations during the OGTT, were measured in 10 patients with duodenal ulcer and in 10 healthy control subjects. The mean responses of GIP and insulin to OGTT were significantly increased in the ulcer patients. During IVGI the responses were normal. The degree of increased GIP response in the patients was positively correlated with the plasma glucose increase during the OGTT. It is postulated that the increased GIP secretion is related to a faster glucose absorption due to rapid gastric emptying in duodenal ulcer patients. No correlation was found between basal and peak gastric acid output and the GIP response in the patients. The data demonstrate that GIP secretion is not defective in duodenal ulcer patients. 相似文献
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10.
Shweta Urva PhD Tamer Coskun MD Corina Loghin MD Xuewei Cui PhD Emily Beebe BS Libbey O'Farrell BS Daniel A. Briere MS Charles Benson MD Michael A. Nauck MD Axel Haupt MD 《Diabetes, obesity & metabolism》2020,22(10):1886-1891
The effect of dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide on gastric emptying (GE) was compared to that of GLP-1RAs in non-clinical and clinical studies. GE was assessed following acute and chronic treatment with tirzepatide in diet-induced obese mice versus semaglutide or long-acting GIP analogue alone. Participants [with and without type 2 diabetes (T2DM)] from a phase 1, 4-week multiple dose study received tirzepatide, dulaglutide or placebo. GE was assessed by acetaminophen absorption. In mice, tirzepatide delayed GE to a similar degree to that achieved with semaglutide; however, these acute inhibitory effects were abolished after 2 weeks of treatment. GIP analogue alone had no effect on GE or on GLP-1's effect on GE. In participants with and without T2DM, once-weekly tirzepatide (≥5 and ≥4.5 mg, respectively) delayed GE after a single dose. This effect diminished after multiple doses of tirzepatide or dulaglutide in healthy participants. In participants with T2DM treated with an escalation schedule of tirzepatide 5/5/10/10 or 5/5/10/15 mg, a residual GE delay was still observed after multiple doses. These data suggest that tirzepatide's activity on GE is comparable to that of selective GLP-1RAs. 相似文献