The Beta Cell Function in NIDDM Patients with Secondary Failure:

Av, Greco; Caputo, Salvatore; Bertoli, A; Ghirlanda, Giovanni

doi:10.1055/s-2007-1003313

Cited by 8 publications

(2 citation statements)

References 7 publications

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“…This was especially true for gliclazide and tolbutamide, which caused a sustained reduction of blood glucose levels without sustained secretion of insulin. Several studies have demonstrated that sulphonylureas exert an antidiabetic effect not only through stimulating insulin release but also by increasing the effect of insulin (Lebovitz, 1984, Beck‐Nielsen et al , 1988). Our present observations may also reflect the involvement of extrapancreatic actions in the blood glucose lowering effect.…”

Section: Discussionmentioning

confidence: 99%

“…The occurrence of secondary failure is also an important problem in the management of NIDDM (Groop et al , 1986; 1989). The causes of the failure of sulphonylurea therapy are still unknown, but one hypothesis is that exhaustion of β‐cells leads to unresponsiveness to these drugs (Greco et al , 1992). Chronic exposure to sulphonylureas is known to have a sup‐pressive effect on β‐cell function in vitro and in vivo (Filipponi et al , 1983; Davalli et al , 1992).…”

Section: Discussionmentioning

confidence: 99%

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Hypoglycaemic and insulinotropic effects of a novel oral antidiabetic agent, (−)‐N‐(trans‐4‐isopropylcyclohexane‐carbonyl)‐d‐phenylalanine (A‐4166)

Ikenoue

Akiyoshi

Fujitani

et al. 1997

British J Pharmacology

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Japan 1 (7)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166), a novel oral hypoglycaemic agent is a non-sulphonylurea insulin secretagogue. 2 We investigated the insulin-releasing action and hypoglycaemic e ect of A-4166 compared to sulphonylureas in vitro and in vivo. 3 A-4166 stimulated insulin secretion from rat freshly isolated pancreatic islets at concentrations from 3610 -6 M to 3610 -4 M in the presence of 2.8 mM glucose. There was no obvious di erence in glucose dependency between the insulinotropic e ect of A-4166 and that of glibenclamide, and no additive or synergistic e ect was observed between these two drugs. 4 A-4166 displaced [ 3 H]-glibenclamide bound to intact HIT-T15 cells in a concentration-dependent manner. The K i value was 4.34+0.04610 77 M, and the displacement potency of A-4166 was between that of glibenclamide and tolbutamide, being similar to that of gliclazide. 5 In fasted beagle dogs, A-4166 showed a dose-dependent hypoglycaemic e ect after oral administration over the range 1 to 10 mg kg 71 . The hypoglycaemic action of A-4166 showed an earlier onset and a shorter duration than that of sulphonylureas. 6 Simultaneous measurement of plasma insulin levels revealed that the hypoglycaemic e ect of A-4166 was caused by a rapid-onset and brief burst of insulin secretion. 7 The pharmacokinetic pro®le of A-4166 was consistent with the changes of the blood glucose and plasma insulin levels. 8 Although the in vitro insulin-releasing e ect of A-4166 was similar to that of sulphonylureas, its hypoglycaemic e ect was more rapid and shorter-lasting, associated with rapid absorption and clearance. Thus, A-4166 may be useful in suppressing postprandial hyperglycaemia in patients with non-insulindependent diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hypoglycaemic and insulinotropic effects of a novel oral antidiabetic agent, (−)‐N‐(trans‐4‐isopropylcyclohexane‐carbonyl)‐d‐phenylalanine (A‐4166)

Ikenoue

Akiyoshi

Fujitani

et al. 1997

British J Pharmacology

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Unmet needs among patients with Type 2 diabetes and secondary failure to oral anti-diabetic agents

Pitocco

Valle

Rossi

et al. 2008

J Endocrinol Invest

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Secondary failure is defined as a deterioration of glucose control in patients with Type 2 diabetes on oral antidiabetic drugs (OAD), mainly due to the progressive decline in beta-cell function and reduction in insulin secretion. The consequent hyperglycemia is the most important determinant for the development of microvascular and macrovascular complications, so that an early recognition of this phenomenon can improve long-term outcomes. The recent lowering of target glycosylated hemoglobin (HbA1c) levels by international guidelines not only emphasises the importance of tight glycemic control, but also means that secondary failure to OAD will occur much sooner and is almost unavoidable. Accordingly, in the last years, new different therapeutic strategies were explored to improve the treatment of this condition. The aim of this review is to examine current approaches for treating patients with secondary failure, barriers to achieving and maintaining glycemic control, and recent evidence for emerging therapies which may represent a valid therapeutic option in subjects failing on oral hypoglycemic agents by acting mainly, but not only, at a beta-cell level. In particular, we will focus on the co-administration of OAD plus a novel drug class known as incretin mimetics (e.g. exenatide and liraglutide), which target insulin secretion, and on thiazolidinediones, which act on insulin resistance. Only incretin-mimetics have a lowering HbA1c action, due to the improvement in beta-cell function, which is coupled to significant weight loss. Even if these new options seem to improve the outcome of secondary failure, further investigation is needed to confirm positive results in the long term.

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Insulin therapy in type 2 diabetes

Davis

Edelman

2004

Medical Clinics of North America

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The Beta Cell Function in NIDDM Patients with Secondary Failure:

Cited by 8 publications

References 7 publications

Hypoglycaemic and insulinotropic effects of a novel oral antidiabetic agent, (−)‐N‐(trans‐4‐isopropylcyclohexane‐carbonyl)‐d‐phenylalanine (A‐4166)

Hypoglycaemic and insulinotropic effects of a novel oral antidiabetic agent, (−)‐N‐(trans‐4‐isopropylcyclohexane‐carbonyl)‐d‐phenylalanine (A‐4166)

Unmet needs among patients with Type 2 diabetes and secondary failure to oral anti-diabetic agents

Insulin therapy in type 2 diabetes

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