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Background: Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associations raise the issue of ‘which SNPs in which populations.’ The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis. Methods: Blood was collected from 208 Saudi subjects with (n=107) and without (n=101) T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT) and GHSR (rs509030 GC) genes. In addition, plasma GHRL levels were measured by a radioimmunoassay. Results: None of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region. Conclusion: Neither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR. [ABSTRACT FROM AUTHOR]

Background: In women with polycystic ovary syndrome (PCOS), despite a high prevalence of insulin resistance, hyperandrogenemia, and disturbances in the secretion of gonadotrophin, the principal causes of biochemical abnormalities and the best endocrine markers for PCOS have not been fully identified. Subjects and methods: Serum levels of insulin, glucose, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, estrogen, sex hormone-binding capacity (SHBG), and other related indices such as homeostasis model assessment, insulin glucose ratios, LH/FSH ratios, and the free androgen index (FAI) were determined and compared in women with PCOS (n = 50) and women without PCOS (n = 50). Results: In multivariate logistic regression analyses, among all insulin resistance indices, only hyperinsulinemia (odds ratio [OR] = 2.6; confidence interval [CI]: 1.3-5.2; P = 0.008) was significantly and independently associated with PCOS when adjusted for body mass index (BMI), hyperandrogenemia, and LH/FSH ratios. The LH/FSH ratio (OR = 5.4; CI: 1.2-23.0, P = 0.03) was the only marker among those indices for inappropriate gonadotrophin secretion that significantly and independently associated with PCOS when adjusted for BMI and hyperinsulinemia. Among those indices for hyperandrogenemia, FAI (OR = 1.1; CI: 1.0-2.7; P = 0.02) and SHBG (OR = 1.2; CI: 1.2-3.4; P = 0.03) were significantly and independently associated with PCOS when adjusted for BMI and hyperinsulinemia. In addition, receiver operating characteristic analysis showed that the best predictive markers for PCOS were insulin (area under the curve [AUC] = 0.944; CI: 0.887-0.989), FAI (AUC = 0.932; CI: 0.895-0.993), SHBG (AUC = 0.924; CI: 0.87-0.978), and LH/FSH ratios (AUC = 0.906; CI: 0.821-0.965). Conclusion: For insulin and LH/FSH ratios, FAI, and SHBG seemed the best predictors and markers for insulin resistance, inappropriate gonadotrophin secretion, and hyperandrogenemia, respectively, with high sensitivity and specificity for identifying Bahraini women with and without PCOS. [ABSTRACT FROM AUTHOR]

1. The activities of a range of enzymes from the glyeolytic and pentose phosphate pathways, tricarboxylic acid cycle and lipogenic pathways have been measured in the mammary glands of rats at different, stages of the lactation cycle and in the lactating sheep mammary gland. 2. Changes of the enzyme activities are considered in the light of constant and specific proportion enzymes; in particular, in relation to the alternative systems for the generation of NADPH in the cytosol. 3. Specifically considered are the metabolic transitions in the rat at parturition and weaning; comparison between lactating sheep and rat mammary gland (which manufacture a similar spectrum of fatty acids from different carbon sources) and a comparison between lactating rat mammary gland and rat adipose tissue. 4. Evidence is adduced from enzyme profiles and flux data that the major source and pathway of generation of NADPH differed in the three tissues, an adaptation dependent upon carbon source and over-all energy requirement of the tissue. Specifically, rat mammary gland has a greater emphasis upon NADPH formation via the pentose phosphate pathway, sheep mammary gland from cytosolic isocitrate dehydrogenase (combined with glutamate dehydrogenase acting as a transhydrogenase system) and adipose tissue showing participation of both pentose phosphate pathway and 'malic' enzyme. 5. The adaptation of mammary tissue to the use of the pentose phosphate pathway or of isocitrate dehydrogenase confers considerable advantage in the ATP yields relative to adipose tissue, where partial generation of NADPH via the 'malic' enzyme necessitates an ATPconsuming reaction. 6. The modification in other satellite systems of lipid synthesis, such as pyruvate carboxylase, citrate cleavage enzyme and glycerol-l-phosphate dehydrogenase, is linked to the relative emphasis on different hydrogen-generating systems, to the source of carbon and to the function of the tissue as a secretory or storage and release tissue. [ABSTRACT FROM AUTHOR]