Anti-obesity and anti-diabetic effects of L-citrulline are sex-dependent.

AIMS: Anti-diabetic and anti-obesity effects of L-citrulline (Cit) have been reported in male rats. This study determined sex differences in response to Cit in Wistar rats. MAIN METHODS: Type 2 diabetes (T2D) was induced using a high-fat diet followed by low-dose of streptozotocin (30 mg/kg) injection. Male and female Wistar rats were divided into 4 groups (n = 6/group): Control, control+Cit, T2D, and T2D + Cit. Cit (4 g/L in drinking water) was administered for 8 weeks. Obesity indices were recorded, serum fasting glucose and lipid profile were measured, and glucose and pyruvate tolerance tests were performed during the Cit intervention. White (WAT) and brown (BAT) adipose tissues were weighted, and the adiposity index was calculated at the end of the study. KEY FINDINGS: Cit was more effective in decreasing fasting glucose (18 % vs. 11 %, P = 0.0100), triglyceride (20 % vs. 14 %, P = 0.0173), and total cholesterol (16 % vs. 11 %, P = 0.0200) as well as decreasing gluconeogenesis and improving glucose tolerance, in females compared to male rats with T2D. Following Cit administration, decreases in WAT weight (16 % vs. 14 % for gonadal, 21 % vs. 16 % for inguinal, and 18 % vs. 13 % for retroperitoneal weight, all P < 0.0001) and increases in BAT weight (58 % vs. 19 %, for interscapular and 10 % vs. 7 % for axillary, all P < 0.0001) were higher in females than male rats with T2D. The decrease in adiposity index was also higher (11 % vs. 9 %, P = 0.0007) in females. SIGNIFICANCE: The anti-obesity and anti-diabetic effects of Cit in rats are sex-dependent, with Cit being more effective in female than male rats.

Metabolic effects of L-citrulline in type 2 diabetes.

The prevalence of type 2 diabetes (T2D) is increasing worldwide. Decreased nitric oxide (NO) bioavailability is involved in the pathophysiology of T2D and its complications. L-citrulline (Cit), a precursor of NO production, has been suggested as a novel therapeutic agent for T2D. Available data from human and animal studies indicate that Cit supplementation in T2D increases circulating levels of Cit and L-arginine while decreasing circulating glucose and free fatty acids and improving dyslipidemia. The underlying mechanisms for these beneficial effects of Cit include increased insulin secretion from the pancreatic ß cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and ß-oxidation, and decreased glyceroneogenesis in the adipose tissue. Thus, Cit has antihyperglycemic, antidyslipidemic, and antioxidant effects and has the potential to be used as a new therapeutic agent in the management of T2D. This review summarizes available literature from human and animal studies to explore the effects of Cit on metabolic parameters in T2D. It also discusses the possible mechanisms underlying Cit-induced improved metabolic parameters in T2D.

Contractions in the Isolated Uterus of a Rat Model of Polycystic Ovary Syndrome Compared to Controls in Adulthood.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women during the reproductive age. Considering disorders reported in women with PCOS, e.g. infertility, pregnancy complications (premature delivery, caesarean section and spontaneous miscarriages), and hormonal disorders, we hypothesized that uterine contractions in PCOS rats may be different from controls. We aimed to compare uterine contractions in PCOS rats with controls. METHODS: Rats in the experimental group were subcutaneously injected with 5 mg of free testosterone on gestational day 20, while controls received solvent. The contractions of isolated uterus in offspring of both groups were recorded by the power lab system, after exposure to carbachol and oxytocin. Two-way analysis of variance was used to compare results between 2 groups. RESULTS: PCOS rats showed more irregular uterine contractions compared to controls. After exposure to carbachol, frequency, and resting tone in the PCOS rats were significantly increased compared to controls (P = 0.004, P = 0.02, respectively). After exposure to oxytocin, the frequency, resting tone and amplitude of rhythmic contractions did not differ between the 2 groups. CONCLUSIONS: Our study indicates irregular uterine contractions and different mechanical responses of isolated uterus in PCOS rats compared to controls.

Are serum nitric oxide metabolites associated with fasting insulin among Iranian adults? (Tehran Lipid and Glucose Study).

AIM: It has been suggested that insulin resistance is associated with altered nitric oxide (NO) homeostasis. There is however no population-based study documenting an association between fasting serum insulin and serum NO metabolites (NOx) with multivariable adjustment. This study was therefore designed to determine the association between serum NOx and fasting insulin levels and insulin resistance/sensitivity indices in a sample of a population-based study in Iran. MATERIALS AND METHODS: This study, performed within the framework of the Tehran Lipid and Glucose Study (TLGS), analyzed the data of 1518 non-diabetic subjects (955 women), aged 20-87 years, who had participated in phase III of the TLGS (2006-2008). Serum NOx concentrations were measured using the Griess method. Fasting serum insulin was measured by the electrochemiluminescence immunoassay method. Multiple regression analysis was used to determine the association between serum NOx concentration and quartiles of insulin and insulin resistance/sensitivity indices (HOMA1-IR, HOMA2-IR, and QUICKI). RESULTS: NOx concentration in women only was weakly correlated with HOMA1-IR (r = 0.07, P = 0.03) and QUICKI (r = -0.07, P = 0.03), whereas no significant association was observed in men (P > 0.05). Marginally significant correlations were also found between serum NOx and fasting insulin concentration (r = 0.062, p = 0.057) and HOMA2-IR (r = 0.063, p = 0.053) in women. NOx concentration differed significantly between quartiles of insulin and insulin resistance/sensitivity indices among women and the total population (P < 0.05), associations which remained significant after age adjustment (P < 0.05), but not after adjustment for other confounding variables (P > 0.05). CONCLUSIONS: Fasting serum insulin level and insulin resistance/sensitivity indices are not associated with serum NOx level after multivariable adjustment.

Pediatric reference values for serum creatinine and estimated glomerular filtration rate in Iranians: Tehran Lipid and Glucose Study.

BACKGROUND: Serum creatinine is the most widely used marker for estimating glomerular filtration rate (GFR). The aim of this study was to determine pediatric reference values for serum creatinine levels and eGFR values using data from a population-based study in Iran. METHODS: Serum creatinine of 1594 subjects, aged 3 - 18 years, participating in phase 4 of the Tehran Lipid and Glucose Study (2008 - 2011) was measured using the conventional Jaffe method. The non-parametric method of Schwartz and Counahan-Barratt equations were used to calculate eGFR. CLSI/IFCC guidelines were used to determine reference values. RESULTS: In both genders, serum creatinine concentration was significantly increased with age and had a positive correlation with age (boys (r = 0.786, n = 778, P < 0.001) and girls (r = 0.638, n = 724, P < 0.001)). In addition, mean serum creatinine concentration was significantly higher in boys, compared to girls (0.86 ± 0.01 vs. 0.80 ± 0.01 mg/dL, P < 0.001). Based on these results, we proposed the following formula: serum creatinine (mg/dL) = k × age (year) + 0.5, where k was 0.03 for boys and 0.02 for girls. CONCLUSIONS: This study presents pediatric reference values in Iranian boys and girls for serum creatinine levels to be 0.6 - 1.20 mg/dL and 0.6 - 1.00 mg/dL and for eGFR values to be 81 - 154 mL/min/1.73 m(2) and 80 - 129 mL/min/1.73 m(2), respectively. These values can be used for diagnostic and therapeutic purposes.

The effects of vitamin d on insulin release from isolated islets of rats.

BACKGROUND: Vitamin D (vit D) affects glucose metabolism. Receptors of vitamin D have been identified in ß cells and studies show that vitamin D deficiency reduces glucose-stimulated insulin secretion (GSIS). OBJECTIVES: The aim of this study was to examine the effect of vitamin D on insulin release from isolated islets of rats. MATERIALS AND METHODS: Islets were isolated from male Wistar rats, weighing 200-250 grams, using the collagenase digestion method. Insulin release was assessed following 24 and 48 hours coincubation of islets with vitamin D (0.1, 1 and 10 nM) and glucose (5.6, 11.1 and 16.7 mM). In addition, islets were preincubated with vitamin D for 24 and 48 hours and GSIS was assessed for one hour in the presence of 5.6 and 16.7 mM glucose. RESULTS: Coincubation of islets with vitamin D (10 nM) and 11.1 mM glucose increased islet insulin release (37.27 ± 3.75 vs. 24.64 ± 2.83 ng/islet/24 hours; P < 0.05), while vitamin D (1 and 10 nM) decreased insulin release in the presence of 16.7 mM glucose (21.14 ± 3.58 and 18.65 ± 3.84 vs. 37.71 ± 4.63 ng/ islet/24 hours; P < 0.05). Islets preincubation with vitamin D (1 and 10 nM) increased GSIS in the presence of 16.7 mM glucose (4.39 ± 0.73 and 4.39 ± 0.63 vs. 2.07 ± 0.43 ng/islet/1 hour; P < 0.05). CONCLUSIONS: Preincubation of islets with vitamin D increased GSIS but decreased insulin release in coincubation with high levels of glucose. Insulin secretion from ß cells in the presence of glucose seems to be related to the dosage of vitamin D and duration of preincubation.