Constance L. Chik

Bio: Constance L. Chik is an academic researcher from University of Alberta. The author has contributed to research in topics: Pinealocyte & Protein kinase C. The author has an hindex of 31, co-authored 108 publications receiving 2558 citations. Previous affiliations of Constance L. Chik include National Institutes of Health & Oregon Health & Science University.

Diagnosis and management of hyperprolactinemia

Abstract: PROLACTIN IS A PITUITARY HORMONE that plays a pivotal role in a variety of reproductive functions. Hyperprolactinemia is a common condition that can result from a number of causes, including medication use and hypothyroidism as well as pituitary disorders. Depending on the cause and consequences of the hyperprolactinemia, selected patients require treatment. The underlying cause, sex, age and reproductive status must be considered. We describe the diagnostic approach and management of hyperprolactinemia in various clinical settings, with emphasis on newer diagnostic strategies and the role of various therapeutic options, including treatment with selective dopamine agonists.

Postpartum Diabetes Screening: adherence rate and the performance of fasting plasma glucose versus oral glucose tolerance test

Abstract: OBJECTIVE To determine the rate of adherence to postpartum glycemic testing in women with gestational diabetes mellitus (GDM) and the performance of fasting plasma glucose (FPG) versus the 75-g oral glucose tolerance test (OGTT) in detecting postpartum glucose intolerance. RESEARCH DESIGN AND METHODS The study was a retrospective cohort of 1,006 women with GDM attending a pregnancy diabetes clinic. RESULTS Postpartum screening was completed in 438 (48%) women. Women nonadherent to testing had higher parity (1.10 vs. 0.87) and were less likely to require insulin for management of their GDM. Among women who were tested, 89 (21%) had an abnormal result, only 25 (28%) of whom were identified by FPG. Factors associated with abnormal postpartum diabetes screening include non-Caucasian ethnicity, previous GDM, higher A1C, and OGTT values during pregnancy and treatment with insulin. CONCLUSIONS The rate of postpartum diabetes screening is low, and FPG lacks sensitivity as a screening test in comparison with OGTT.

Mechanisms of action of a second generation growth hormone-releasing peptide (Ala-His-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2) in rat anterior pituitary cells.

Abstract: The mechanism by which GH-releasing peptides elicit GH secretion has remained largely unknown. In this study, the effects of a second generation GH-releasing peptide, Ala-His-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2(GHRP-1), on cAMP, intracellular Ca2+ ([Ca2+]i), and GH release were examined using rat pituitary gland static monolayer cell cultures. It was found that GHRP-1 increased GH release in a dose-dependent manner up to 3-fold, while having no effect on cAMP levels. In contrast, simultaneous elevations of cAMP and GH were observed after treatment with GHRH. To further define the underlying mechanism of GHRP-1-mediated GH release, its effect on [Ca2+]i was determined using a fluorescent Ca2+ indicator, fura-2. GHRP-1 dose dependently increased [Ca2+]i up to 45.5 nM +/- 5.6 nM. A similar elevation of [Ca2+]i was observed after GHRH treatment. Similar to GHRH, GHRP-1-induced increases in [Ca2+]i and GH release were inhibited by somatostatin. Furthermore, the GHRP-1-induced increases in [Ca2+]i and GH were also suppressed by nifedipine. The interaction between the voltage-dependent Ca2+ channels and GHRP-1 was investigated in cells maximally stimulated by KCl. The addition of GHRP-1 had no effect on the KCl-stimulated GH release. To investigate the possible interaction between the adenylyl cyclase pathway and GHRP-1, cells were maximally stimulated with forskolin or (Bu)2cAMP. Addition of GHRP-1 stimulated GH release beyond that observed using cAMP elevating agents. Similar results were obtained in the presence of a protein kinase C, 4 beta-phorbol 12-myristate 13-acetate (PMA). The GHRP-1-stimulated GH release was additive to that observed with PMA stimulation. Based on these findings, it was concluded that 1) GHRP-1 treatment leads to an increase in [Ca2+]i; 2) unlike GHRH, GHRP-1 releases GH via a Ca(2+)-dependent, cAMP-independent mechanism; 3) GHRP-1-induced increases in [Ca2+]i and GH release are sensitive to somatostatin inhibition; and 4) cAMP-elevating agents and PMA have an additive effect on the GHRP-1-stimulated GH release, indicating these agents stimulate GH release via a mechanism separate from that of GHRP-1.

Impact of gestational diabetes mellitus and high maternal weight on the development of diabetes, hypertension and cardiovascular disease: a population‐level analysis

Abstract: Aims To examine the association between gestational diabetes mellitus (GDM) and high maternal weight and the risk of development of chronic disease. Methods Women with singleton deliveries between April 1999 and March 2010 in Alberta, Canada, were categorized according to pre-pregnancy weight (overweight ≥ 91 kg) and GDM status. Obstetric and neonatal outcomes, as well as the long-term incidence of maternal diabetes, hypertension and cardiovascular disease were examined. Results Of 240 083 women, 213 765 (89%) had no GDM and were not overweight (reference group), 17 587 (7.3%) were overweight only, 7332 (3%) had GDM only and 1399 (0.6%) had GDM and were overweight. Significant differences in Caesarean section rates, induction rates and birthweight were observed across the four groups. During a median follow-up of 5.3 years, diabetes incidence was 36% in the GDM and overweight, 18.8% in the GDM only, 4.8% in the overweight only and 1.1% in the reference group. With respect to hypertension and cardiovascular disease, the GDM and overweight group had the highest rates (26.8% and 3.1%, respectively) and the reference group had the lowest rates (5.8% and 1.0%, respectively). However, rates were similar in the GDM only (14.9% and 1.9%, respectively) and overweight only groups (14.9% and 1.5%, respectively). Conclusions Not surprisingly, the presence of both high maternal weight and GDM compounds the risk of developing diabetes. However, the association between overweight alone and GDM alone and hypertension and cardiovascular disease appears similar suggesting a need for effective interventions to manage both these conditions to improve the health of these patients.

Hyperprolactinemia caused by lactation and pituitary adenomas is associated with altered serum calcium, phosphate, parathyroid hormone (PTH), and PTH-related peptide levels

Abstract: PRL stimulates systemic release of PTH-related peptide (PTHrP) in animals. To determine whether hyperprolactinemia causes PTHrP release in humans, we studied the relationship between PRL and PTHrP in lactating women and patients with PRL-producing pituitary adenomas. Thirty-three lactating women and 16 patients with pituitary adenomas were paired with healthy age- and sex-matched controls. Serum total calcium, albumin, phosphate, PRL, intact PTH, and PTHrP were measured. Mean calcium and phosphate levels were higher in lactating women than in control subjects [2.39 +/- 0.01 vs. 2.35 +/- 0.01 mmol/L (P < 0.01) and 1.33 +/- 0.03 vs. 1.13 +/- 0.02 mmol/L (P << 0.001), respectively]. Mean PTH was lower (2.49 +/- 0.24 vs. 3.17 +/- 0.23 pmol/L; P < 0.04) and mean PTHrP was higher than control values (0.93 + 0.08 vs. 0.38 +/- 0.04 pmol/L; P << 0.001). PRL correlated negatively with PTH (P < 0.02) and positively with PTHrP (P < 0.05). Mean calcium, phosphate, and PTH levels were not different between patients wit...

Ghrelin is a growth-hormone-releasing acylated peptide from stomach.

Abstract: Small synthetic molecules called growth-hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through GHS-R, a G-protein-coupled receptor for which the ligand is unknown. Recent cloning of GHS-R strongly suggests that an endogenous ligand for the receptor does exist and that there is a mechanism for regulating GH release that is distinct from its regulation by hypothalamic growth-hormone-releasing hormone (GHRH). We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. The purified ligand is a peptide of 28 amino acids, in which the serine 3 residue is n-octanoylated. The acylated peptide specifically releases GH both in vivo and in vitro, and O-n-octanoylation at serine 3 is essential for the activity. We designate the GH-releasing peptide 'ghrelin' (ghre is the Proto-Indo-European root of the word 'grow'). Human ghrelin is homologous to rat ghrelin apart from two amino acids. The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin.

Ghrelin: Structure and Function

Abstract: Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it "ghrelin," after a word root ("ghre") in Proto-Indo-European languages meaning "grow." Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.

International Union of Pharmacology. XLVIII. Nomenclature and Structure-Function Relationships of Voltage-Gated Calcium Channels

Abstract: The family of voltage-gated sodium channels initiates action potentials in all types of excitable cells. Nine members of the voltage-gated sodium channel family have been characterized in mammals, and a 10th member has been recognized as a related protein. These distinct sodium channels have similar structural and functional properties, but they initiate action potentials in different cell types and have distinct regulatory and pharmacological properties. This article presents the molecular relationships and physiological roles of these sodium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties.