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Insulinotropic Agents

Rapid Acting Insulinotropic Agents: Restoration Of Early Insulin Secretion As A Physiologic Approach To Improve Glucose Control

Rapid Acting Insulinotropic Agents: Restoration Of Early Insulin Secretion As A Physiologic Approach To Improve Glucose Control

The loss of early insulin secretion appears to be a critical event in the deterioration in glucose tolerance during the development of type 2 diabetes. There is therefore a strong rationale for developing new antidiabetic agents aimed at restoring or replacing early prandial insulin secretion and thereby curbing mealtime glucose excursions in patients with type 2 diabetes. Four such new agents are either now available (repaglinide and nateglinide) or in clinical development (KAD-1229 and BTS 67 582). Preclinical studies suggest that each of these new insulinotropic agents share a common receptor/effector mechanism with the sulfonylureas (SUs) but that each may have distinct characteristics that differentiate them from the SUs and from each other. Nateglinide and KAD-1229 clearly stimulate biphasic insulin secretion in vitro and in vivo and their effects are rapidly reversible, whereas the effects of repaglinide and BTS 67 582 are prolonged well beyond their removal from perfusion media in vitro or their clearance in vivo. Available data from human studies indicate that the pharmacokinetics of repaglinide and nateglinide are similar, i.e., they are both rapidly absorbed and eliminated, but consistent with findings from animal studies, the insulinotropic and glucose-lowering effects of repaglinide are slower in onset and more prolonged than those of nateglinide. Repaglinide and nateglinide have been shown to be safe and well-tolerated in patients with type 2 diabetes and to produce clinically-meaningful reductions of HbA1c, both alone and in combination with agents with complementary modes of action (e.g., metformin and thiazolidinediones). Because these new agents can potentially bring patients to near normoglycemia without an undue risk of hypoglycemia, they are import Continue reading >>

Insulinotropic Agent Id-1101 (4-hydroxyisoleucine) Activates Insulin Signaling In Rat.

Insulinotropic Agent Id-1101 (4-hydroxyisoleucine) Activates Insulin Signaling In Rat.

Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat. @article{Broca2004InsulinotropicAI, title={Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat.}, author={Christophe Broca and Vincent Breil and C{\'e}line Cruciani-Guglielmacci and Mich{\`e}le Manteghetti and Christine Rouault and Michel Derouet and Salwa Rizkalla and Bernard Pau and Pierre Petit and G{\'e}rard Ribes and Alain Ktorza and Ren{\'e} Gross and G{\'e}rard Reach and Mohammed Taouis}, journal={American journal of physiology. Endocrinology and metabolism}, year={2004}, volume={287 3}, pages={E463-71}} American journal of physiology. Endocrinology and ID-1101 (4-hydroxyisoleucine), an amino acid extracted from fenugreek seeds, exhibits an interesting glucose-dependent insulin-stimulating activity. The present study was undertaken to investigate a possible extrapancreatic effect of ID-1101 on insulin signaling and action besides its previously described insulinotropic action. Insulin-sensitizing effects of ID-1101 were investigated in rat in vivo by three different approaches: 1) using euglycemic hyperinsulinemic clamps in two different ratCONTINUE READING Continue reading >>

Future Perspectives For Insulinotropic Agents In The Treatment Of Type 2 Diabetes-dpp-4 Inhibitors And Sulphonylureas [2010]

Future Perspectives For Insulinotropic Agents In The Treatment Of Type 2 Diabetes-dpp-4 Inhibitors And Sulphonylureas [2010]

Future perspectives for insulinotropic agents in the treatment of type 2 diabetes-DPP-4 inhibitors and sulphonylureas This translation tool is powered by Google. FAO is not responsible for the accuracy of translations. Future perspectives for insulinotropic agents in the treatment of type 2 diabetes-DPP-4 inhibitors and sulphonylureas [2010] Future perspectives for insulinotropic agents in the treatment of type 2 diabetes-DPP-4 inhibitors and sulphonylureas The introduction of dipeptidyl-peptidase IV inhibitors (DPP-4 inhibitors) brought a novel class of insulinotropic agents into the treatment options for type 2 diabetes. This paper compares the actions, clinical efficacy and safety of sulphonylureas with those of the DPP-4 inhibitors. First, the mode of action of both classes of antidiabetic agents is described. Then clinical studies for both substances in monotherapy and combination therapies are compared concerning their effects on glycaemic parameters and long-term duration of action. Hypoglycaemia incidence and other adverse effects are compared and data on cardiovascular parameters and endpoints are summarized. The effects of sulphonylureas and DPP-4 inhibitors on beta-cell function and beta-cell mass are highlighted. The present and future indications for both sulphonylureas and DPP-4 inhibitors are discussed. [insulinotropic agents, oral therapy, DPP-4 inhibitors, incretin based therapy, sulfonylureas, noninsulin-dependent diabetes mellitus] The introduction of dipeptidyl-peptidase IV inhibitors (DPP-4 inhibitors) brought a novel class of insulinotropic agents into the treatment options for type 2 diabetes. This paper compares the actions, clinical efficacy and safety of sulphonylureas with those of the DPP-4 inhibitors. First, the mode of action of both class Continue reading >>

Characterization Of 111in-labeled Glucose-dependent Insulinotropic Polypeptide As A Radiotracer For Neuroendocrine Tumors

Characterization Of 111in-labeled Glucose-dependent Insulinotropic Polypeptide As A Radiotracer For Neuroendocrine Tumors

[Lys37(DTPA)]N-acetyl-GIP1-42 could be labeled with 111In with a specific activity (now referred to as molar activity 29 ) of up to 1.2 TBq/mol. Radiochemical purity exceeded 95% as determined by RP-HPLC and ITLC, resulting in a final molar activity exceeding 142.5 MBq/g or 712.5MBq/nmol when starting with 150 MBq [111In]Cl3. Figure 2a shows the HPLC analysis of the labeling mixture. 111In-EDTA eluted with a retention time of 3 minutes, whereas 111In labeled [Lys37(DTPA)]N-acetyl-GIP1-42 had a retention time of 14 minutes. After 12 minutes, a very small impurity (<2%) eluted from the column. Since GIP is known to be prone to inactivation by dipeptidyl peptidase IV (DPP IV), the stability of [Lys37(111In-DTPA)]N-acetyl-GIP1-42 was analyzed in human serum. The results of this stability analysis are shown in Fig. 2b and c . Up to 4 hours of incubation in human serum, the [Lys37(111In-DTPA)]N-acetyl-GIP1-42 remained intact. After 24 hours of incubation in human serum, 73% of the activity was still found as intact radiolabeled peptide, as determined by HPLC. (a) Radiochemical purity analysis of [Lys37(111In-DTPA)]N-acetyl-GIP1-42 as determined by HPLC, immediately after labeling. (b) HPLC profile of 111In-GIP after 24 hours of incubation in human serum. (c) Overview of stability behavior after various incubation times in human serum. In this study, we investigated the potential of [Lys37(111In-DTPA)]N-acetyl-GIP1-42 for NET detection. The tracer showed GIPR-mediated binding to BHK-GIPR positive cells and NES2Y cells, and to isolated islets in vitro. Optimal GIPR-mediated tumor targeting of BHK-GIPR positive tumors in vivo, was observed 1 hour post injection using a peptide dose of 0.2 g (0.04 nmol). Furthermore, both BHK-GIPR transfected tumors and NES2Y tumors were visuali Continue reading >>

Insulinotropic Actions Of Nateglinide In Type 2 Diabetic Patients And Effects On Dipeptidyl Peptidase-iv Activity And Glucose-dependent Insulinotropic Polypeptide Degradation

Insulinotropic Actions Of Nateglinide In Type 2 Diabetic Patients And Effects On Dipeptidyl Peptidase-iv Activity And Glucose-dependent Insulinotropic Polypeptide Degradation

Insulinotropic actions of nateglinide in type 2 diabetic patients and effects on dipeptidyl peptidase-IV activity and glucose-dependent insulinotropic polypeptide degradation 1 School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK (Correspondence should be addressed to A M McKillop; Email: [email protected] ) 2009 European Society of Endocrinology 2009 Nateglinide restores early-phase insulin secretion to feeding and reduces postprandial hyperglycaemia in type 2 diabetes. This study evaluated the effects of nateglinide on dipeptidyl peptidase-IV (DPP-IV) activity and glucose-dependent insulinotropic polypeptide (GIP) degradation. Blood samples were collected from type 2 diabetic subjects (n=10, fasting glucose 9.361.2 mmol/l) following administration of oral nateglinide (120 mg) 10 min prior to a 75 g oral glucose load in a randomised crossover design. Plasma glucose reached 18.21.7 and 16.71.7 mmol/l at 90 min in control and placebo groups (P<0.001). These effects were accompanied by prompt 32% inhibition of DPP-IV activity after 10 min (19.91.6 nmol/ml per min, P<0.05), reaching a minimum of 1.90.1 nmol/ml per min at 120 min (P<0.001) after nateglinide. Insulin and C-peptide levels increased significantly compared with placebo, to peak after 90 min at 637.6163.9 pmol/l (P<0.05) and 11.81.4 mg/l (P<0.01) respectively. DPP-IV-mediated degradation of GIP was significantly less in patients receiving nateglinide compared with placebo. Inhibition of DPP-IV activity corresponded with a time- and concentration-dependent inhibitory effect of nateglinide on DPP-IV-mediated truncation of GIP(142) to GIP(342) in vitro. Comparison of in vitro inhibition of DPP-IV by nateglinide and vildagliptin revealed IC50 values of 17.1 and 2.1 M Continue reading >>

Targeting Postprandial Hyperglycemia: A Comparative Study Of Insulinotropic Agents In Type 2 Diabetes

Targeting Postprandial Hyperglycemia: A Comparative Study Of Insulinotropic Agents In Type 2 Diabetes

Targeting Postprandial Hyperglycemia: A Comparative Study of Insulinotropic Agents in Type 2 Diabetes Internal Medicine/Endocrinology, University of New Mexico, Albuquerque, New Mexico 87131 Address all correspondence and requests for reprints to: Mary F. Carroll, M.D., Internal Medicine/Endocrinology, MSC10 5550, 1 University of New Mexico, Albuquerque, New Mexico 87131. Search for other works by this author on: Internal Medicine/Endocrinology, University of New Mexico, Albuquerque, New Mexico 87131 Search for other works by this author on: Internal Medicine/Endocrinology, University of New Mexico, Albuquerque, New Mexico 87131 Search for other works by this author on: Internal Medicine/Endocrinology, University of New Mexico, Albuquerque, New Mexico 87131 Search for other works by this author on: Internal Medicine/Endocrinology, University of New Mexico, Albuquerque, New Mexico 87131 Search for other works by this author on: The Journal of Clinical Endocrinology & Metabolism, Volume 88, Issue 11, 1 November 2003, Pages 52485254, Mary F. Carroll, Absalon Gutierrez, Marygrace Castro, Dechen Tsewang, David S. Schade; Targeting Postprandial Hyperglycemia: A Comparative Study of Insulinotropic Agents in Type 2 Diabetes, The Journal of Clinical Endocrinology & Metabolism, Volume 88, Issue 11, 1 November 2003, Pages 52485254, This study was designed to compare the efficacy of three insulinotropic agents in the control of postprandial hyperglycemia in type 2 diabetes. Fifteen subjects with noninsulin-requiring type 2 diabetes were admitted to the General Clinical Research Center on four separate occasions. During the control study and following 710 d on each study medication, daylong glucose profiles were performed to investigate the effects of the assigned medication on pos Continue reading >>

Drug-drug And Food-drug Pharmacokinetic Interactions With New Insulinotropic Agents Repaglinide And Nateglinide.

Drug-drug And Food-drug Pharmacokinetic Interactions With New Insulinotropic Agents Repaglinide And Nateglinide.

This review describes the current knowledge on drug-drug and food-drug interactions with repaglinide and nateglinide. These two meglitinide derivatives, commonly called glinides, have been developed for improving insulin secretion of patients with type 2 diabetes mellitus. They are increasingly used either in monotherapy or in combination with other oral antihyperglycaemic agents for the treatment of type 2 diabetes. Compared with sulfonylureas, glinides have been shown to (i) provide a better control of postprandial hyperglycaemia, (ii) overcome some adverse effects, such as hypoglycaemia, and (iii) have a more favourable safety profile, especially in patients with renal failure. The meal-related timing of administration of glinides and the potential influence of food and meal composition on their bioavailability may be important. In addition, some food components (e.g. grapefruit juice) may cause pharmacokinetic interactions. Because glinides are metabolised via cytochrome P450 (CYP) 3A4 isoenzyme, they are indeed exposed to pharmacokinetic interactions. In addition to CYP3A4, repaglinide is metabolised via CYP2C8, while nateglinide metabolism also involves CYP2C9. Furthermore, both compounds and their metabolites may undergo specialised transport/uptake in the intestine, another source of pharmacokinetic interactions. Clinically relevant drug-drug interactions are those that occur when glinides are administered together with other glucose-lowering agents or compounds widely coadministered to diabetic patients (e.g. lipid-lowering agents), with drugs that are known to induce (risk of lower glinide plasma levels and thus of deterioration of glucose control) or inhibit (risk of higher glinide plasma levels leading to hypoglycaemia) CYP isoenzymes concerned in their met Continue reading >>

Ep2877201a4 - A Liquid Formulation Of Long-acting Insulin And Insulinotropic Peptide - Google Patents

Ep2877201a4 - A Liquid Formulation Of Long-acting Insulin And Insulinotropic Peptide - Google Patents

EP2877201A4 - A liquid formulation of long-acting insulin and insulinotropic peptide - Google Patents A liquid formulation of long-acting insulin and insulinotropic peptide EP2877201A4 EP20130822545 EP13822545A EP2877201A4 EP 2877201 A4 EP2877201 A4 EP 2877201A4 EP 20130822545 EP20130822545 EP 20130822545 EP 13822545 A EP13822545 A EP 13822545A EP 2877201 A4 EP2877201 A4 EP 2877201A4 Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.) Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.) Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.) A61MEDICAL OR VETERINARY SCIENCE; HYGIENE A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-dr

Effects Of Insulinotropic Agents On Cationic Fluxes In Islet Cells

Effects Of Insulinotropic Agents On Cationic Fluxes In Islet Cells

Effects of Insulinotropic Agents on Cationic Fluxes in Islet Cells Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 119) In the stimulus-secretion coupling for insulin release, a remodelling of ionic fluxes in the pancreatic B-cell may represent the essential link between the site of identification of secretagogues and the site of release of secretory granules (1). This paper reviews the participation of several cations (K+, Na+, H+, Mg2+, Ba2+, and Ca2+) in the process of insulin release and in delineating the influence of insulinotropic agents, especially glucose, upon the handling of such cations. Islet CellInsulin ReleaseIncrease Glucose ConcentrationInsulin OutputInsulinotropic Action These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves. This is a preview of subscription content, log in to check access. Unable to display preview. Download preview PDF. Malaisse, W.J., et al. (1978). Ann. N.Y. Acad. Sci., 307, 562 PubMed CrossRef Google Scholar Sehlin, J. and Tljedal, I.-B. (1974). J. Physiol. (Lond.), 242, 505 Google Scholar Boschero, A.C., et al. (1977), FEBS Lett., 83, 151 PubMed CrossRef Google Scholar Malaisse, W.J., et al. (1978). Pflgers Arch. 373, 237 PubMed CrossRef Google Scholar Henquin, J.C. (1978). Nature, 271, 271 PubMed CrossRef Google Scholar Boschero, A.C. and Malaisse, W.J. (1979). Amer. J. Physiol (In press) Google Scholar Dean, P.M. and Matthews, E.K. (1968). Nature, 219, 389 PubMed CrossRef Google Scholar Pace, C.S. and Price, S. (1972). Biochem. Biophys. Res. Commun., 46, 1557. PubMed CrossRef Google Scholar Meissner, H.P. and Atwater, I.J. (1976). Horm. Metab. Res., 8, 11. PubMed CrossRef Google Scholar Bos Continue reading >>

Glucose-dependent Insulinotropic Receptor (ipr028336)

Glucose-dependent Insulinotropic Receptor (ipr028336)

Glucose-dependent insulinotropic receptor (IPR028336) Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. However, recent research has identified certain pharmacological targets that could be investigated to find, for example, new potential cannabinoid receptors or channels [ PMID: 21079038 , PMID: 17906678 , PMID: 20117132 ]. GPR18 IPR028335 [ PMID: 21595653 , PMID: 20346144 ], GPR55 IPR028334 [ PMID: 17876302 , PMID: 17876300 ], GPR119 IPR028336 [ PMID: 20117132 ] show little structural similarity to CB1 and CB2 receptors, but they respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands [ PMID: 21079038 ]. However, because they do not fulfill all of the cannabinoid receptor criteria defined by IUPHAR, the classification of these proteins remains a contentious issue due to conflicting pharmacological results. As a result, they remain classified as putative endogenous agonists by IUPHAR [ PMID: 21079038 ]. This entry represents glucose-dependent insulinotropic receptor, also known as G protein-coupled receptor 119. It is expressed predominantly in the pancreas and gastrointestinal tract in rodents and humans, as well as in the brain in rodents [ PMID: 16517404 ]. It has been shown to be involved in the control of glucose-dependent insulin release and glucagon-like peptide 1 release, respectively [ PMID: 15607732 , PMID: 17289847 ], which caused a reduction in food intake and body weight gain in rats [ PMID: 16517404 ]. GPR119 has also been shown to regulate incretin and insulin hormone secretion [ PMID: 18724386 , PMID: 19009545 , PMID: 19282326 ], behaving as a glucose-dependent insulinotropic receptor. As a result, Continue reading >>

Jci -postprandial Stimulation Of Insulin Release By Glucose-dependent Insulinotropic Polypeptide (gip). Effect Of A Specific Glucose-dependent Insulinotropic Polypeptide Receptor Antagonist In The Rat.

Jci -postprandial Stimulation Of Insulin Release By Glucose-dependent Insulinotropic Polypeptide (gip). Effect Of A Specific Glucose-dependent Insulinotropic Polypeptide Receptor Antagonist In The Rat.

Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid peptide produced by K cells of the mammalian proximal small intestine and is a potent stimulant of insulin release in the presence of hyperglycemia. However, its relative physiological importance as a postprandial insulinotropic agent is unknown. Using LGIPR2 cells stably transfected with rat GIP receptor cDNA, GIP (1-42) stimulation of cyclic adenosine monophosphate (cAMP) production was inhibited in a concentration-dependent manner by GIP (7-30)-NH2. Competition binding assays using stably transfected L293 cells demonstrated an IC50 for GIP receptor binding of 7 nmol/liter for GIP (1-42) and 200 nmol/liter for GIP (7-30)-NH2, whereas glucagonlike peptide-1 (GLP-1) binding to its receptor on ++betaTC3 cells was minimally displaced by GIP (7-30)-NH2. In fasted anesthetized rats, GIP (1-42) stimulated insulin release in a concentration-dependent manner, an effect abolished by the concomitant intraperitoneal administration of GIP (7-30)-NH2 (100 nmol/ kg). In contrast, glucose-, GLP-1-, and arginine-stimulated insulin release were not affected by GIP (7-30)-NH2. In separate experiments, GIP (7-30)-NH2 (100 nmol/kg) reduced postprandial insulin release in conscious rats by 72%. It is concluded that GIP (7-30)-NH2 is a GIP-specific receptor antagonist and that GIP plays a dominant role in mediating postprandial insulin release. Continue reading >>

They Are Available As Monotherapy Or Combination Therapies, With The Latter Involving Two (or, Less Commonly, Three) Antidiabetic Drugs And/or

They Are Available As Monotherapy Or Combination Therapies, With The Latter Involving Two (or, Less Commonly, Three) Antidiabetic Drugs And/or

Antidiabetic drugs (with the exception of insulin) are all pharmacological agents that have been approved for hypoglycemic treatment in type 2 diabetes mellitus (DM). If lifestyle modifications (weight loss, dietary modification, and exercise) do not sufficiently reduce A1C levels (target level: ∼ 7%), pharmacological treatment with antidiabetic drugs should be initiated. These drugs may be classified according to their mechanism of action as insulinotropic or non-insulinotropic. They are available as monotherapy or combination therapies, with the latter involving two (or, less commonly, three) antidiabetic drugs and/or insulin. The exact treatment algorithms are reviewed in the treatment section of diabetes mellitus. The drug of choice for all type 2 diabetic patients is metformin. This drug has beneficial effects on glucose metabolism and promotes weight loss or at least weight stabilization. In addition, numerous studies have demonstrated that metformin can reduce mortality and the risk of complications. If metformin is contraindicated, not tolerated, or does not sufficiently control blood glucose levels, another class of antidiabetic drug may be administered. Most antidiabetic drugs are not recommended or should be used with caution in patients with moderate or severe renal failure or other significant comorbidities. Oral antidiabetic drugs are not recommended during pregnancy or breastfeeding. Continue reading >>

Insulinotropic Agents From Medicinal Plants

Insulinotropic Agents From Medicinal Plants

Research Article,J Pharm Sci Emerg Drugs Vol: 2 Issue: 2 Insulinotropic Agents from Medicinal Plants University College of Pharmaceutical Sciences, Kakatiya University, Warangal-506009, AP, India University College of Pharmaceutical Sciences, Kakatiya University, Warangal-506009, Telangana, India Received: August 12, 2014 Accepted: October 06, 2014 Published: October 11, 2014 Citation: Balekari U, Veeresham C. (2014) Insulinotropic Agents from Medicinal Plants. J Pharm Sci Emerg Drugs 2:1. doi:10.4172/2380-9477.1000101 Insulinotropic Agents from Medicinal Plants Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from lack of insulin secretion or insulin sensitivity or both. Enhancement of insulin levels and insulin sensitivity is the primary target in the treatment of diabetes. Current treatment options, such as dietary modifications, oral hypoglycemic drugs and insulin have limitations of their own. In view of this, several medicinal plants have been studied for anti-diabetic activity using various in vitro and in vivo methods. Therefore, researchers have been focusing research to find an effective and safe antihyperglycemic drug for clinical use from natural sources. The present review emphasizes on phytochemicals and medicinal plant extracts with insulinotropic activity to reduce hyperglycemia . This review also categorized phytochemicals and plant extracts based on their mode of action like insulin secretagogues, insulin mimetics and both. Keywords: Diabetes; Insulin; Insulin secretion; Insulin sensitivity; Medicinalplants; Hyperglycemia; Insulinotropic; Insulin secretagogue; Insulinmimetic Continue reading >>

Glucose-dependent And Glucose-sensitizing Insulinotropic Effect Of Nateglinide: Comparisonto Sulfonylureas And Repaglinide

Glucose-dependent And Glucose-sensitizing Insulinotropic Effect Of Nateglinide: Comparisonto Sulfonylureas And Repaglinide

Glucose-dependent and Glucose-sensitizing Insulinotropic Effect of Nateglinide: Comparisonto Sulfonylureas and Repaglinide Metabolic and Cardiovascular Diseases, Novartis Institute for Biomedical Research, 556 Morris Avenue, Summit, NJ 07901, USA Received 6 December 2000; Accepted 18 January 2001 Copyright 2001 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The following is the list of published articles that have cited the current article. Shiling Hu, and Shuya Wang, Effect of insulinotropic agent nateglinide on Kv and Ca2+ channels in pancreatic -cell, European Journal of Pharmacology, vol. 427, no. 2, pp. 97104, 2001. View at Publisher View at Google Scholar Fm Ashcroft, Rd Carr, Jb Hansen, P Wahl, It Christensen, and Amk Hansen, Differential interactions of nateglinide and repaglinide on the human beta-cell sulphonylurea receptor 1, Diabetes, vol. 51, no. 9, pp. 27892795, 2002. View at Publisher View at Google Scholar Shiling Hu, Interaction of nateglinide with KATP channel in -cells underlies its unique insulinotropic action, European Journal of Pharmacology, vol. 442, no. 1-2, pp. 163171, 2002. View at Publisher View at Google Scholar L Groop, K Lahti, C Saloranta, P de Pablos-Velasco, E Pecher, P Brunel, and C Guitard, Nateglinide improves early insulin secretion and controls postprandial glucose excursions in a prediabetic population, Diabetes Care, vol. 25, no. 12, pp. 21412146, 2002. View at Publisher View at Google Scholar G Grunberger, S Gupta, Je Foley, V Fonseca, and S Shen, Addition of nateglinide to rosiglitazone monotherapy suppresses mealtime hyperglycem Continue reading >>

Rapid Acting Insulinotropic Agents: Restoration Of Early Insulin Secretion As A Physiologic Approach To Improve Glucose Control.

Rapid Acting Insulinotropic Agents: Restoration Of Early Insulin Secretion As A Physiologic Approach To Improve Glucose Control.

Rapid acting insulinotropic agents: restoration of early insulin secretion as a physiologic approach to improve glucose control. Novartis Pharmaceuticals Corporation, 59 Route 10, East Hanover, New Jersey 07936, USA. [email protected] The loss of early insulin secretion appears to be a critical event in the deterioration in glucose tolerance during the development of type 2 diabetes. There is therefore a strong rationale for developing new antidiabetic agents aimed at restoring or replacing early prandial insulin secretion and thereby curbing mealtime glucose excursions in patients with type 2 diabetes. Four such new agents are either now available (repaglinide and nateglinide) or in clinical development (KAD-1229 and BTS 67 582). Preclinical studies suggest that each of these new insulinotropic agents share a common receptor/effector mechanism with the sulfonylureas (SUs) but that each may have distinct characteristics that differentiate them from the SUs and from each other. Nateglinide and KAD-1229 clearly stimulate biphasic insulin secretion in vitro and in vivo and their effects are rapidly reversible, whereas the effects of repaglinide and BTS 67 582 are prolonged well beyond their removal from perfusion media in vitro or their clearance in vivo. Available data from human studies indicate that the pharmacokinetics of repaglinide and nateglinide are similar, i.e., they are both rapidly absorbed and eliminated, but consistent with findings from animal studies, the insulinotropic and glucose-lowering effects of repaglinide are slower in onset and more prolonged than those of nateglinide. Repaglinide and nateglinide have been shown to be safe and well-tolerated in patients with type 2 diabetes and to produce clinically-meaningful reductions of HbA1c Continue reading >>

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