Importance of Early Insulin Secretion

Hollander, Priscilla; Schwartz, Sherwyn; Gatlin, Marjorie; Haas, Stephen J.; Zheng, Hongjie; Foley, James E.; Dunning, Beth E.

doi:10.2337/diacare.24.6.983

Cited by 122 publications

(86 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Glipizide and glyburide were considerably less effective than nateglinide in reducing glucose excursions but both produced substantial hypoglycaemia that did not resolve within the 6-h experimental period [24]. Similar results with nateglinide have been found in the monkey in vivo, as highlighted in this supplement [34], and in recent clinical studies [35,36,37].…”

Section: Insulin Secretion In Vitrosupporting

confidence: 78%

The mechanisms underlying the unique pharmacodynamics of nateglinide

Boettcher

Dunning

2003

Diabetologia

View full text Add to dashboard Cite

Nateglinide, a D-phenylalanine derivative, belongs to a new group of insulinotropic agents with rapid onset and short duration of action. These agents have been developed to reduce the risk of hypoglycaemia associated with pharmacological control and to decrease the likelihood of pancreatic beta-cell exhaustion. Nateglinide mediates the release of insulin from beta-cells by binding to the sulphonylurea receptors, which leads to the closure of ATP-sensitive K + channels. Increasing evidence from receptor binding, mechanistic and in vitro and in vivo insulin studies indicate unique pharmacodynamic and pharmacokinetic properties with nateglinide that are distinct from those of sulphonylureas. The time required by nateglinide to close beta-cell K ATP channels is comparable to that of glyburide but threefold and fivefold faster than repaglinide and glimepiride, respectively. Furthermore, its effects are rapidly reversed with an off-rate at the K ATP channel twice as fast as that of glyburide and glimepiride and five times faster than repaglinide. This results in a rapid and short insulin response characteristic of the physiological pattern of post-mealtime insulin release. Internalisation into beta-cells is not required for the action of nateglinide. Given that the kinetic profile of the agent is associated with selective enhancement of early-phase insulin secretion, nateglinide is expected to minimise post-meal hyperglycaemia with minimal propensity for hypoglycaemia. [Diabetologia (2003)

show abstract

Section: Insulin Secretion In Vitrosupporting

confidence: 78%

The mechanisms underlying the unique pharmacodynamics of nateglinide

Boettcher

Dunning

2003

Diabetologia

View full text Add to dashboard Cite

show abstract

“…Nateglinide, a D-phenylalanine derivative, is characterized by a rapid and short-lasting glucose dependent stimulatory effect on insulin secretion [36]. The therapeutic impact of this compound has been recently explored [37,38]. As compared to glibenclamide, nateglinide had a greater effect on mealtime glucose excursions, though glibenclamide was associated with a greater reduction of [29] fasting plasma glucose concentrations [38].…”

Section: Restoration Of Early Insulin Release In Type 2 Diabetic Patimentioning

confidence: 99%

“…The therapeutic impact of this compound has been recently explored [37,38]. As compared to glibenclamide, nateglinide had a greater effect on mealtime glucose excursions, though glibenclamide was associated with a greater reduction of [29] fasting plasma glucose concentrations [38]. In Type 2 diabetic patients, nateglinide appeared to selectively increase early insulin release which resulted in a lower overall insulin exposure relative to glibenclamide.…”

Section: Restoration Of Early Insulin Release In Type 2 Diabetic Patimentioning

confidence: 99%

Loss of early insulin secretion leads to postprandial hyperglycaemia

2003

View full text Add to dashboard Cite

Aims/Hypothesis. A loss of early-phase insulin response is common in Type 2 diabetic patients and in people with impaired glucose metabolism. It is hypothesized that this alteration is not simply a marker for the risk of developing diabetes, rather it is a an important pathogenetic mechanism causing excessive postprandial hyperglycaemia. Methods. Relevant literature on the epidemiology, physiopathology, and therapeutic intervention related to loss of early insulin secretion and postprandial hyperglycaemia has been analysed. Results. In response to intravenous glucose, insulin secretion is biphasic. This behaviour translates as a rapid release of insulin into the blood stream in response to the ingestion of carbohydrates or a mixed meal. The rapid increase in portal insulin concentration and the avid binding of the hormone to its receptor on liver cell membranes, account for a prompt suppression of endogenous glucose production and reduction of the rate of increase in plasma glucose concentrations. This has been supported by experimental studies carried out in both animals and humans: the selective abolition of early insulin secretion in healthy subjects results in impaired glucose tolerance, excessive glucose excursions, and possible hampering of the thermic effects of ingested carbohydrates. In nondiabetic subjects, the loss of early insulin secretion is a determinant for developing diabetes. The critical role of the early-phase insulin response in determining postprandial hyperglycaemia, is supported by an amelioration of glucose tolerance by restoring the acute rise in plasma insulin concentrations after the ingestion of both glucose and a mixed meal. This amelioration in plasma glucose profile can prevent late hyperglycaemia and hyperinsulinaemia. Conclusion/interpretation. Therapeutic approaches aimed at restoring a physiological pattern of insulin secretion could prove effective in reducing postprandial glucose excursions particularly in the early stage of Type 2 diabetes. [Diabetologia (2003)

show abstract

“…In this study, nateglinide, one of the "glinides" compounds, selectively enhanced early meal-induced insulin secretion and thus improved mealtime glucose control. Consistent with the more physiological nature of nateglinide, the overall insulin exposure is relatively lower than that produced by sulfonylurea medication in type 2 diabetes [14,15]. We have previously described that nateglinide improved glycemic response after oral glucose load in obese individuals with impaired glucose tolerance or early type 2 diabetes by improvement of early phase insulin secretion without increasing the total amount of insulin (i.e., area under the curve) [17,18].…”

Section: Discussionmentioning

confidence: 76%

“…Nateglinide is a novel highly physiologic, mealtime glucose regulator recently approved for the treatment of type 2 diabetes [14,15]. Nateglinide selectively enhances early meal-induced insulin secretion and thus improves postprandial hyperglycemia.…”

mentioning

confidence: 99%

Efficacy and Adverse Effects of Nateglinide in Early Type 2 Diabetes. Comparison with Voglibose in a Cross-over Study

et al. 2006

View full text Add to dashboard Cite

Abstract. An open-label prospective cross-over trial was performed to compare the efficacy and adverse effects of nateglinide with those of voglibose on Japanese early type 2 diabetes (who were oral hypoglycemic agent naïve and whose HbA 1C levels were between 7.0 and 7.9% before treatment). Fourteen patients received 270 mg/day of nateglinide and 15 patients received 0.6 mg/day of voglibose. After 12 weeks of either therapy, the drugs were switched and treatment was continued for another 12 weeks. After 3-month treatment with each drug, HbA 1C value decreased significantly (baseline HbA 1C 7.24 ± 0.42%, 6.70 ± 0.47% with nateglinide: p<0.01, 6.93 ± 0.62% with voglibose: p<0.05) but the difference in the effect between nateglinide and voglibose was not significant (p = 0.121). Symptoms related to hypoglycemia (e.g., increased appetite, palpitation, sweating, tremor) were scarcely observed with either voglibose or nateglinide treatments. Abdominal fullness/borborygmi was frequently reported, with variable severity, by patients on voglibose but this was absent or mild in those on nateglinide. After completion of both arms of the study, more patients favored nateglinide than voglibose. Our results suggest that nateglinide is an effective and safe drug in the treatment of early type 2 diabetes, similar to voglibose.

show abstract

Importance of Early Insulin Secretion

Cited by 122 publications

References 17 publications

The mechanisms underlying the unique pharmacodynamics of nateglinide

The mechanisms underlying the unique pharmacodynamics of nateglinide

Loss of early insulin secretion leads to postprandial hyperglycaemia

Efficacy and Adverse Effects of Nateglinide in Early Type 2 Diabetes. Comparison with Voglibose in a Cross-over Study

Contact Info

Product

Resources

About