Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dipeptidyl peptidase-IV (DPP-IV) regulates metabolism by degrading incretins involved in nutritional regulation. Metformin and pioglitazone improve insulin sensitivity whereas glyburide promotes insulin secretion. Zucker diabetic rats were treated with these antidiabetic agents for 2 weeks and DPP-IV activity and expression were determined. Serum DPP-IV activity increased whereas tissue activity decreased as the rats aged. Treatment of rats with metformin, pioglitazone, and glyburide did not alter DPP-IV mRNA expression in liver or kidney. Metformin and pioglitazone significantly (P<0.05) reduced serum DPP-IV activity and glycosylated hemoglobin. Glyburide did not lower DPP-IV activity or glycosylated hemoglobin. Regression analysis showed serum DPP-IV activity correlated with glycosylated hemoglobin (r=0.92) and glucagon-like peptide-1 levels (r=-0.49). Metformin, pioglitazone, and glyburide had no effect on serum DPP-IV activity in vitro, indicating these are not competitive DPP-IV inhibitors. We propose the in vivo inhibitory effects observed with metformin and pioglitazone on serum DPP-IV activity results from reduced DPP-IV secretion.
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PMID:Reduced serum dipeptidyl peptidase-IV after metformin and pioglitazone treatments. 1546 87

There are many new orally administered agents to treat type 2 diabetes. Sulfonylureas and meglitinides stimulate insulin secretion. Metformin has been joined by thiazolidinediones to reduce insulin resistance. Disaccharidase inhibitors slow glucose uptake after a meal. Beta-3 agonists and agents that augment glucagon-like peptide activity are promising new agents in the effort to not only control glucose levels but also restrain weight gain. The future treatment of diabetes will require multiple drugs working in concert to normalize blood glucose.
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PMID:Advances in diabetes for the millennium: drug therapy of type 2 diabetes. 1564 14

Metformin has been shown to increase glucagon-like peptide-1 (GLP-1) levels after an oral glucose load in obese non-diabetic subjects. In order to verify if this effect of the drug was also present in obese Type 2 diabetic patients who have never been treated with hypoglycemic drugs, 22 Type 2 diabetic and 12 matched non-diabetic obese patients were studied. GLP-1 was measured before and after a 100 g glucose load at baseline, after a single oral dose of 850 mg of metformin, and after 4 weeks of treatment with metformin 850 mg three times daily. Post-load GLP-1 levels were significantly lower in diabetic patients. A single dose of metformin did not modify GLP-1 levels. After 4 weeks of treatment, fasting GLP-1 increased in diabetic patients (3.8 vs 4.9 pmol/l; p<0.05), while the incremental area under the curve of GLP-1 significantly increased in both diabetic [93.6 (45.6-163.2) vs 151.2 (36.0-300.5) pmol x min/l; p<0.05] and non-diabetic [187.2 (149.4-571.8) vs 324.0 (238.2-744.0) pmol x min/l; p<0.05] subjects. In conclusion, GLP-1 levels after an oral glucose load in obese type 2 diabetic patients were increased by 4 weeks of metformin treatment in a similar fashion as in obese subjects with normal glucose tolerance.
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PMID:Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without Type 2 diabetes. 1588 27

Drug treatment of 2 diabetes is intended to normalize glycosylated hemoglobin levels (HbA(1c)<6.5%) and thereby prevent the development of micro- and macrovascular complications. Oral antidiabetic agents target the metabolic abnormalities that cause diabetes. The two principal families of oral antidiabetic agents - insulin sensitizers and insulin secretagogues - can be taken together. Thiazolidinediones or glitazones (insulin sensitizers) improve peripheral tissue sensitivity to insulin. Metformin (an insulin sensitizer) reduces hepatic glucose production. Sulfonylureas and meglitinides (insulin secretagogues) stimulate insulin secretion and can cause hypoglycemia. GLP-1 (Glucagon-Like Peptide-1) analogs and DPP-IV (dipeptidyl-peptidase-IV) inhibitors are new drug classes currently under development.
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PMID:[Drug treatment of type 2 diabetes]. 1725 75

Sitagliptin, a novel orally-active dipeptidyl-peptidase (DPP-4) inhibitor has been introduced into type 2 diabetes therapy. Sitagliptin inhibits the degradation of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), as well as that of other regulatory peptides important for glucose homeostasis. It reduces haemoglobin A1c (HbA1c), fasting and postprandial glucose by glucose- dependent stimulation of insulin secretion and inhibition of glucagon secretion. Sitagliptin is weight neutral. Indirect measures show a possible improvement of beta-cell function. Sitagliptin does not cause hypoglycemia when compared to metformin or placebo. Metformin, which has a different unique mechanism, has been used in type 2 diabetes for approximately 50 years. Metformin improves insulin resistance and is the first-line antidiabetic drug in use today. The combination of a DPP-4 inhibitor with metformin allows a broad and complementary spectrum of antidiabetic actions. This combination does not increase the risk of hypoglycaemia nor does it promote weight gain, an adverse effect of various other oral antidiabetic combinations. This article gives an overview of the data available on the combined antidiabetic effects of metformin and sitagliptin.
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PMID:Sitagliptin with metformin: profile of a combination for the treatment of type 2 diabetes. 1798 21

Treatment of type 2 diabetes includes lifestyle adaptations and drug treatment with the recent availability of many new substances. Metformin is the best first option at present due to its efficacy, its neutral effect on weight, its security profile and its cost. In addition, metformin can be associated with any other antidiabetic agent. Sulfonylureas remain the best choice for combination with metformin although their effectiveness on glucose control decrease with time more rapidly compared with glitazones. The GLP-1 (glucagon-like peptide 1) analogues and DPP-4 (di-peptidyl-peptidase-4) inhibitors are effective but need long-term evaluation of their security profile. Insulin can be used when the different oral options have failed.
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PMID:[Metformin role in the treatment of type 2 diabetes in 2008]. 1863 62

Vildagliptin is a potent and selective inhibitor of dipeptidyl peptidase-IV (DPP-4), orally active, that improves glycemic control in patients with type 2 diabetes (T2DM) primarily by enhancing pancreatic (alpha and beta) islet function. Thus vildagliptin has been shown both to improve insulin secretion and to suppress the inappropriate glucagon secretion seen in patients with T2DM. Vildagliptin reduces HbA(1c) when given as monotherapy, without weight gain and with minimal hypoglycemia, or in combination with the most commonly prescribed classes of oral hypoglycemic drugs: metformin, a sulfonylurea, a thiazolidinedione, or insulin. Metformin, with a different mode of action not addressing beta-cell dysfunction, has been used for about 50 years and still represents the universal first line therapy of all guidelines. However, given the multiple pathophysiological abnormalities in T2DM and the progressive nature of the disease, intensification of therapy with combinations is typically required over time. Recent guidelines imply that patients will require pharmacologic combinations much earlier to attain and sustain the increasingly stringent glycemic targets, with careful drug selection to avoid unwanted adverse events, especially hypoglycemia. The combination of metformin and vildagliptin offers advantages when compared to currently used combinations with additive efficacy and complimentary mechanisms of action, since it does not increase the risk of hypoglycemia and does not promote weight gain. Therefore, by specifically combining these agents in a single tablet, there is considerable potential to achieve better blood glucose control and to improve compliance to therapy.
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PMID:Combination treatment in the management of type 2 diabetes: focus on vildagliptin and metformin as a single tablet. 1882 67

Postprandial lipemia has emerged as an independent risk factor for coronary artery disease. In this systematic review we examined the effect of the medications used for the management of diabetes, obesity and dyslipidemia on postprandial lipemia. It should be mentioned that no standardization exists for a test meal and for the duration of observation postprandially to allow for direct comparisons between the published studies. Type 2 diabetes mellitus and insulin resistance are associated with enhanced postprandial lipemia. Insulin is effective in reducing both fasting and post prandial total triglyceride levels as well as triglycerides contained in the triglyceride-rich lipoprotein sub-fractions. Additionally, the newer rapid-acting insulin analogues seem to be more effective in the reduction of postprandial lipemia than the short-acting human insulins. Acarbose ameliorates postprandial lipemia and reduces the atherogenic chylomicron and very low density lipoprotein remnants. Metformin reduces both fasting and postprandial triglyceridemia, fasting and post-prandial free fatty acids and may increase the concentrations of the high density lipoprotein cholesterol. Sulfonylureas reduce fasting and postprandial triglyceride levels while data on the effect on high density lipoprotein levels are inconsistent. The effect of meglitinides on postprandial lipid metabolism is neutral. Rosiglitazone decreases fasting and postprandial free fatty acids but has no significant effect on fasting and postprandial triglycerides. Pioglitazone has additional beneficial effects on lipid metabolism because it reduces postprandial free fatty acids, fasting and postprandial triglycerides and increases high density lipoprotein cholesterol levels. Limited available data suggest that glucagon-like peptide-1 analogues and vildagliptin reduce postprandial lipemia through reduction of intestinally-derived triglycerides. No data exist on the effect of sitagliptin on postprandial lipemia. Orlistat improves postprandial lipemia by reducing the absorption of the dietary fat; no data exist on the effect of sibutramine and rimonabant on the metabolism of lipids in the postprandial state.
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PMID:The effects of medications used for the management of diabetes and obesity on postprandial lipid metabolism. 1899 2

Diabetes is a complex disease involving multiple organs with dysregulation in glucose and lipid metabolism. Hepatic insulin insensitivity can contribute to elevated fasting glucose levels and impaired glucose tolerance in individuals with diabetes. Several currently available therapeutics address defects at the liver. Metformin inhibits glucose production, potentially through effects on AMPK. Thiazolidinediones activate PPAR-gamma and improve hepatic insulin sensitivity, primarily through indirect effects on lipid metabolism. Insulin analogs and secretagogues suppress glucose production and increase liver glucose utilization by both direct and indirect hepatic actions. Incretins, incretin mimetics, and dipeptidyl peptidase-4 inhibitors reduce postprandial hepatic glucose production by increasing insulin secretion and limiting glucagon release, as well as through possible direct effects on the liver. Pramlintide reduces the increase in plasma glucagon that occurs following a meal in individuals with diabetes, and may thereby suppress inappropriate stimulation of liver glucose production. Many other hepatic targets are being considered which may lead to alternative strategies for the treatment of diabetes. This review focuses on currently available therapeutics which target insulin resistance in the liver.
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PMID:Current strategies for the inhibition of hepatic glucose production in type 2 diabetes. 1927 23

In normal subjects, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are responsible for 70% of the insulin response during a meal; but in diabetic subjects and other insulin-resistant conditions, the incretin effect is impaired. Polycystic ovary syndrome (PCOS) is associated with insulin resistance, and the pathophysiologic mechanisms behind PCOS resemble those of type 2 diabetes mellitus; therefore, women with PCOS may have alterations in the incretin hormone response. Metformin is widely used in the treatment of both type 2 diabetes mellitus and PCOS. Metformin may exert some of its effect on glucose metabolism by increasing GLP-1 biosynthesis and secretion and thereby increasing the incretin effect. The objective of the study was to measure incretin hormone secretion in women with PCOS and to evaluate the effect of metformin treatment. Cross-sectional comparison of 40 women with PCOS (19 lean and 21 obese) and 26 healthy control women (9 lean and 17 obese) and longitudinal evaluation of the effects of 8 months of metformin 1000 mg twice daily in women with PCOS were performed. Plasma concentrations of GIP and GLP-1 were determined frequently during a 75-g glucose tolerance test, and insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp. The incretin hormone response did not differ between subjects with and without PCOS. Subgroup analysis showed lower GIP (area under the curve [AUC]) levels in obese women with PCOS compared with obese control women (P < .05) and compared with lean women with PCOS (P < .05). Metformin increased GIP (AUC) and GLP-1 (AUC) in lean women with PCOS (P < .05), and a similar trend was seen in the obese women (P = .07). The GIP secretion is attenuated in obese women with PCOS, whereas treatment with metformin increases the levels of both GIP and GLP-1 in women with PCOS.
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PMID:Incretin hormone secretion in women with polycystic ovary syndrome: roles of obesity, insulin sensitivity, and treatment with metformin. 1937 79


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