Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of islet GPR40 protein in the pathogenesis of diabetes is unclear. We explored the influence of GPR40 protein levels on hormone secretion in islets from two rat models of spontaneous type 2 diabetes displaying either hyperlipidaemia or hyperglycaemia. GPR40 expression was analysed by confocal microscopy, Western blot and qPCR in islets from preobese Zucker (fa/fa) rats, diabetic Goto-Kakizaki (GK) rats, and controls. Confocal microscopy of control islets showed expression of GPR40 protein in insulin, glucagon and somatostatin cells. GPR40 expression was strongly increased in islets of hyperlipidaemic fa/fa rats and coincided with a concentration-related increase in palmitate-induced release of insulin and glucagon and its inhibition of somatostatin release. Conversely, hyperglycaemic GK islets displayed an extremely faint expression of GPR40 as did high-glucose-cultured control islets. This was reflected in abolished palmitate-induced hormone response in GK islets and high-glucose-cultured control islets. The palmitate antagonist rosiglitazone promoted reappearance of GPR40 in high-glucose-cultured islets and served as partial agonist in glucose-stimulated insulin release. GPR40 protein is abundantly expressed in pancreatic islets and modulates stimulated hormone secretion. Mild hyperlipidaemia in obesity-prone diabetes creates increased GPR40 expression and increased risk for an exaggerated palmitate-induced insulin response and lipotoxicity, a metabolic situation suitable for GPR40 antagonist treatment. Chronic hyperglycaemia creates abrogated GPR40 expression and downregulated insulin release, a metabolic situation suitable for GPR40 agonist treatment to avoid glucotoxicity. GPR40 protein is interactively modulated by both free fatty acids and glucose and is a promising target for pharmacotherapy in different variants of type 2 diabetes.
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PMID:GPR40 protein levels are crucial to the regulation of stimulated hormone secretion in pancreatic islets. Lessons from spontaneous obesity-prone and non-obese type 2 diabetes in rats. 2391 64

An increased risk of colorectal cancer (CRC) is associated with a western style diet, particularly hyperlipidemia. The expression of G-protein coupled receptor 40 (GPR40), a membrane-bound receptor for long-chain fatty acids (LCFAs), was examined in 36 cases of subserosal-invading CRC and compared with clinicopathological parameters as well as triglyceride (TG) and low-density lipoprotein (LDL) levels in the blood. All patients with CRC expressed GPR40, which was positively associated with blood TG levels (P<0.0001) but not with blood LDL levels. GPR40 expression was positively associated with nodal metastasis, distant metastasis (particularly to the liver), stage and poor prognosis. Patients with high GPR40 expression and high TG levels had comparatively worse survival outcomes compared with patients with low GPR40 expression and low TG levels. The results of the present study suggest that activation of GPR40 may be associated with the progression and prognosis of CRCs. High levels of GPR40 and/or concurrent high levels of GPR40 and TG may be a risk for CRC progression.
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PMID:Expression of long-chain fatty acid receptor GPR40 is associated with cancer progression in colorectal cancer: A retrospective study. 2980 99