The clinical response to these oral agents varies among individuals, and genetic predisposition
within nitric oxide synthase 1 adaptor protein (NOS1AP) has been suggested [1].
Neuronal nitric oxide synthase (nNOS) is a member of the nitric oxide synthase (NOSs) family
that also includes endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase
(iNOS) [2]. NOSs null mice all demonstrated insulin resistance [3-7]. Insulin signal pathway
(phosphatidylinositol-3 kinase (P
论文范文http://www.chuibin.com/ I3K)-protein kinase B (AKT)-NOS axis) has been implicated本文来自辣.文,论-文·网原文请找腾讯324.9114
in brain insulin resistance [5]. NO derived from nNOS plays a role in facilitating glucose uptake
and insulin sensitivity [3,6]. Moreover, it inhibits central sympathetic outflow and counteracts
sympathetic vasoconstriction [7]. Besides, nNOS in pancreatic beta cell has been shown to
2+
play a role in insulin release through induction of intracellular Ca [8].
Nitric oxide synthase 1 adaptor protein (NOS1AP), also known CAPON, is localized primarily
in the mitochondria and cytoplasm; and can inhibit nNOS function via binding to nNOS PDZ
motif [9]. Currently, variants in NOS1AP were found to be associated with type 2 diabetes
mellitus [10,11]. It is unknown whether or not binding of NOS1AP to nNOS will affect the
insulin signal pathway. Nor is it clear if the common variation in NOS1AP influences insulin
secretion and/or insulin resistance. In this study, we determined the variant and the efficacy of
repaglinide (one of the oral anti-diabetic meglitinides that stimulates insulin secretion by
+
blocking ATP-sensitive K channels to modulate intracellular calcium in beta cells [12]) in
newly diagnosed Shanghai Chinese type 2 diabetes patients who had been treated with
repaglinide for 24 weeks.
rials and methods
ts and Study Design
Newly diagnosed type 2 diabetes patents, diagnosed on the basis of the World Health
Organization criteria[13], were recruited from outpatient clinics of ten hospitals in Shanghai.
The patients were between 30 and 70 years old with entry glycated hemoglobin value >6.5%,
and did no antihyperglycemic therapies prior to the study. Exclusion criteria include diabetic
ketoacidosis, nonketotic hyperosmolar coma, chronic diabetic complication with fasting
plasma glucose (FPG) >13 mmol/L (234 mg/dL) and/or 2 h postprandial plasma glucose (2-h
PG) >18 mmol/L (324 mg/dL) (details were described previously)[13]. We recruited 104
patients (69 men, 35 women) and treated them with repaglinide for 24 weeks. Repaglinide was
administrated initially in a mealtime dosage of 0.5 mg and later increased stepwise to 1, 1.5,
and 2 mg for patients who failed to achieve glycemic targets of fasting plasma glucose < 7
mmol/L (126 mg/dL) and/or 2 h plasma glucose < 11 mmol/L (200 mg/dL). Experimental
protocols used in this study were approved by the institutional review board of Shanghai Jiao
Tong University Affiliated Sixth People's Hospital. Subjects were given informed written
consent.
opometric measurements本文来自辣.文,论-文·网原文请找腾讯3249,114
The general anthropometric parameters considered for the study were height (m), weight (kg),
waist and hip circumferences (cm). All patients were measured at baseline of the study and 24
weeks after the initiation of the repaglinide therapy. The Body mass index (BMI) and waist–
2
hip ratio were calculated as weight/height and waist/hip, respectively.
al laboratory tests
Overnight, fasting and 2-h blood samples (following a 75 g oral glucose tolerance test (OGTT))
were collected. Glycated hemoglobin
论文范文http://www.chuibin.com/ values were determined by high-performance liquid
chromatography with a Bio-Rad Variant II hemoglobin testing system (Bio-Rad Laboratories,
Hercules, CA, USA). Insulin resistance and beta cell function were assessed by homeostasis
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