Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 9-year-old castrated male European shorthair cat with insulin-resistant diabetes was referred with the preliminary diagnosis of pituitary-dependent hyperadrenocorticism, based on measurements of urinary corticoids. Further studies revealed not only resistance of plasma concentrations of cortisol, adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) to suppression by a low dose of dexamethasone, but also elevated plasma concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I). Pituitary imaging with dynamic contrast-enhanced computed tomography demonstrated an enlarged pituitary gland and an adenoma. The cat underwent trans-sphenoidal hypophysectomy after which the insulin resistance disappeared. On histopathological and immunocytochemical examination of the surgical specimen a double adenoma was found, consisting of a corticotroph adenoma and a somatotroph adenoma separated by unaffected pituitary tissue.
 ...
PMID:Somatotroph and corticotroph pituitary adenoma (double adenoma) in a cat with diabetes mellitus and hyperadrenocorticism. 1500 81

The Pituitary Society in conjunction with the European Neuroendocrine Association held a consensus workshop to develop guidelines for diagnosis and treatment of the co-morbid complications of acromegaly. Fifty nine pituitary specialists (endocrinologists, neurosurgeons and cardiologists) assessed the current published literature on acromegaly complications in light of recent advances in maintaining tight therapeutic control of GH hypersecretion. The impact of elevated GH levels on cardiovascular disease, hypertension, diabetes, sleep apnea, colon polyps, bone disease, reproductive disorders, and neuropsychologic complications were considered. Guidelines are proposed for effective management of these complications in the context of overall acromegaly control. When appropriate, requirements for prospective evidence-based studies and surveillance database development are enunciated. Effective management of co-morbid acromegaly complications will lead to improved morbidity and mortality in acromegaly.
 ...
PMID:Diagnosis and treatment of acromegaly complications. 1505 79

Pituitary adenylate cyclase activating polypeptide (PACAP) is a ubiquitous neuropeptide in the central and peripheral nervous systems. Previously we reported that PACAP38 is localized in pancreatic islets and serves as an endogenous amplifier of glucose-induced insulin secretion. PACAP activates Gs-cAMP system, stimulates voltage-dependent Ca(2+) channels, and increases cytosolic Ca(2+) concentration in beta-cells. On the other hand, PAC1 receptor is expressed in adipocytes. PACAP enhances insulin-stimulated glucose uptake in an adipocyte cell-line, 3T3-L1 cells. PACAP does not alter the tyrosine phosphorylation of insulin receptor and IRS-1, but increases the activity of PI-3 kinase, a distal site of insulin signaling. PACAP also promotes differentiation of 3T3-L1 cells from fibroblasts to adipocytes. In GK rats, an animal model of type 2 diabetes, daily i.p. injection of PACAP38 (6 pmol/kg) from the age of 3 weeks prevents development of hyperglycemia between 3 to 8 weeks. These results demonstrate that PACAP enhances glucose-stimulated insulin secretion in islets, enhances insulin action inadipocytes, and prevents hyperglycemia in diabetic animals. This finding presents a possible therapeutic use of PACAP in the treatment of diabetes.
 ...
PMID:[Physiological and therapeutic roles of PACAP in glucose metabolism and diabetes]. 1505 42

mRNA levels of kinin B1 and B2 receptors were determined in HPA axis of type 1 (STZ-induced) and type 2 diabetic rats (ZDF and obese Zucker rats). B2 mRNA levels were elevated in hypothalamus of STZ-induced diabetic (STZ-D) and ZDF rats. Pituitary B2 mRNA levels were elevated in ZDF and obese rats. Adrenal B2 mRNA level was attenuated in STZ-D rats. Kinin B1 receptor may not play a role in HPA axis in diabetes since its expression was unchanged. Enhanced mRNA expression of B2 receptors in hypothalamus of STZ-D and ZDF rats parallels a rise in plasma glucose and reflect a functional relationship. Enhanced pituitary B2 mRNA in type 2 and reduced adrenal in type 1 diabetes account for a differential pattern in release of transmitters.
 ...
PMID:Expression of kinin receptor mRNA in the HPA axis of type 1 and type 2 diabetic rats. 1517 Dec 37

For proper development and tissue homeostasis, cell cycle progression is controlled by multilayered mechanisms. Recent studies using knock-out mice have shown that animals can develop relatively normally with deficiency for each of the G1/S-regulatory proteins, D-type and E-type cyclins, cyclin-dependent kinase 4 (Cdk4), and Cdk2. Although Cdk4-null mice show no embryonic lethality, they exhibit specific endocrine phenotypes, i.e. dwarfism, infertility, and diabetes. Here we have demonstrated that Cdk4 plays an essential non-redundant role in postnatal proliferation of the anterior pituitary. Pituitaries from wild-type and Cdk4-null embryos at embryonic day 17.5 are morphologically indistinguishable with similar numbers of cells expressing a proliferating marker, Ki67, and cells expressing a differentiation marker, growth hormone. In contrast, anterior pituitaries of Cdk4-null mice at postnatal 8 weeks are extremely hypoplastic with markedly decreased numbers of Ki67+ cells, suggesting impaired cell proliferation. Pituitary hyperplasia induced by transgenic expression of human growth hormone-releasing hormone (GHRH) is significantly diminished in the Cdk4+/- genetic background and completely abrogated in the Cdk4-/- background. Small interfering RNA (siRNA)-mediated knockdown of Cdk4 inhibits GHRH-induced proliferation of GH3 somato/lactotroph cells with restored expression of GHRH receptors. Cdk4 siRNA also inhibits estrogen-dependent cell proliferation in GH3 cells and closely related GH4 cells. In contrast, Cdk6 siRNA does not diminish proliferation of these cells. Furthermore, Cdk4 siRNA does not affect GHRH-induced proliferation of mouse embryonic fibroblasts or estrogen-dependent proliferation of mammary carcinoma MCF-7 cells. Taken together, Cdk4 is dispensable for prenatal development of the pituitary or proliferation of other non-endocrine tissues but indispensable specifically for postnatal proliferation of somato/lactotrophs.
 ...
PMID:Cdk4 is indispensable for postnatal proliferation of the anterior pituitary. 1545 44

It has been reported that adult patients with growth hormone deficiency (GHD) have increased risk factors for cardiovascular disorders in Western countries. However, data on this issue in Japan have not been fully investigated. To clarify the situation on this issue in Japan, a nationwide questionnaire survey was conducted by Study Group of Hypothalamo-Pituitary Disease, and medical records of 863 adult patients were recruited. The incidences of complications and risk factors for cardiovascular diseases were compared between GH deficient patients (GHD, n = 494) and GH intact patients (GHI, n = 369). The incidence of myocardial infarction was higher in GHD (1.2%) than in GHI (0.8%), but not significantly. The incidences of angina pectoris and liver dysfunction were significantly higher in GHD than in GHI (2.8 vs 0.8%, p = 0.048, and 11.9 vs 5.5%, p<0.0001, respectively). The prevalences of obesity and hyperlipidemia (HL) were significantly higher in GHD (p = 0.004, p<0.001, respectively). Combinations of HL plus diabetes mellitus (DM) or hypertension (HT) were more common in GHD than in GHI (HL + DM; 7.2 vs. 2.9%, HL + HT; 10.9 vs. 2.9%). These results indicated that GH deficiency have an increased prevalence of cardiovascular risk factors in Japanese similar to Western countries, and suggested that GH supplement therapy may be needed to reduce those complications.
 ...
PMID:Complications in adults with growth hormone deficiency--a survey study in Japan. 1551 82

Diabetes is associated with increased basal hypothalamo-pituitary-adrenal (HPA) activity and impaired stress responsiveness. Previously, we demonstrated that the HPA response to hypoglycemia is significantly impaired in diabetic rats. In this study our goals were to 1) differentiate between the effects of hyperinsulinemia and those of hypoglycemia per se, and 2) establish whether diabetes lowers peak stress responses. Normal and streptozotocin-diabetic rats were subjected to hyperinsulinemic-euglycemic glucose clamps to evaluate central and peripheral responses. These were compared with peak ACTH and corticosterone responses to restraint and hypoglycemia. Hyperinsulinemia increased CRH and vasopressin mRNA, and plasma ACTH and corticosterone in normal and diabetic rats. In normal animals, insulin-induced activation of ACTH and corticosterone was lower than the responses during either restraint or hypoglycemia. In contrast, ACTH and corticosterone activation in diabetic rats was similar with all three stressors. Pituitary-adrenal axis activation in diabetic animals was also much lower compared with that in normal controls. The response to hyperinsulinemia (euglycemia) was associated with increases in glucocorticoid receptor mRNA in the anterior pituitary and paraventricular nucleus. Hippocampal mineralocorticoid receptor mRNA expression was increased in normal, but not in diabetic, animals. We speculate that the ability to appropriately match the HPA response to the potency of a stressor is related to the ability to alter hippocampal mineralocorticoid receptor expression. In diabetes, this ability is impaired; hence, maximal HPA activation is greatly diminished. This is a novel observation that may have important implications in the treatment of impaired counterregulatory mechanisms in human diabetes.
 ...
PMID:Insulin alone increases hypothalamo-pituitary-adrenal activity, and diabetes lowers peak stress responses. 1556 37

Expression of the diabetes (db/db) mutation in C57BL/KsJ mice suppresses the female pituitary-gonadal axis via progressive cytolipidemic disruption of hypophyseal gonadotropin release, culminating in premature involution of the reproductive tract and manifest infertility. The current studies define the systemic, endocrine, cytochemical and structural apoptotic changes that result from pituitary hypercytolipidemia induced by db/db mutation expression in this Type II diabetes-obesity syndrome (DOS) model. Adult female C57BL/KsJ control (+/? genotype) and db/db littermates were monitored for systemic and cellular alterations in LH-, FSH- and gonadal steroid-secretion, and coincident pituitary apoptosis, as indexed by TUNEL labeled 3' nuclear DNA-fragmentation, associated with cytolipid depositions. Obesity, hyperglycemia and hyperinsulinemia characterized all db/db-mutants relative to +/? groups. Serum progesterone (P) and estradiol (E2) concentrations were suppressed in db/db mutants coincident with decreased plasma LH and FSH concentrations relative to +/? values. Cytochemical analysis of anterior (AP) pituitary cell subtypes indicated that db/db mutants demonstrated prominent hypercytolipidemia relative to +/? pituitary cytoarchitecture. Cytolipidemic vacuoles were localized within protein vesiculated db/db hypophyseal basophilic and acidophilic cell populations. Hypophyseal cytoadiposity in db/db AP cells was co-localized with prominent cellular apoptotic TUNEL labeling of nuclear 3'-DNA fragments in cells demonstrating vesicular depopulation and cytolytic vacuolization. These data represent the first demonstration of co-localized hypercytolipidemic and cytoapoptotic disruptive events occurring concurrently in a hypopituitary-hypogonadal syndrome model following expression of the Type II (NIDDM) diabetes-obesity syndrome in db/db-mutants. The coincident and progressive vascular-, interstitial- and cyto-lipidemic alterations in hypophyseal cytoarchitecture correlated with the concurrent apoptotic disruption of pituitary endocrine cytoarchitecture and supressed gonadal steroid synthesis, influences which collectively contribute to the premature involution of the pituitary-gonadal axis in C57BL/KsJ- db/db mice.
Pituitary 2004
PMID:Hypophyseal lipoapoptosis: diabetes (db/db) mutation-associated cytolipidemia promotes pituitary cellular disruption and dysfunction. 1563 92

The contributions to our present knowledge and understanding of diabetes insipidus are briefly surveyed. Though a disease presenting with polyuria and thirst had been recognized since Antiquity, it was not until the 17. Century the distinction was made between diabetes insipidus and diabetes mellitus. At the beginning of the 20. Century almost nothing was known about the function of the pituitary. It was generally believed that diabetes insipidus was a renal disease. Two clinical observations in 1912 suggested an association between the hypophysis and diabetes insipidus. This view was supported by the recognition in 1913 that extract of the posterior lobe of the pituitary was effective in diabetes insipidus. Despite much evidence to the contrary, it was assumed that the antidiuretic hormone was produced in the intermediate lobe of the pituitary. Around 1950 it was finally established that 'the posterior lobe hormones' are in fact secreted in the hypothalamus. At the same time the antidiuretic hormone was isolated and synthesized. More recently, progress within genetics has made it possible to characterize in details other rare types of diabetes insipidus.
Pituitary 2004
PMID:Diabetes insipidus: historical aspects. 1563 96

Expression of the diabetes (db/db) mutation in C57BL/KsJ mice results in functional suppression of the female pituitary-gonadal axis accompanied by premature utero-ovarian cytolipoatrophy. Cellular gluco- and lipo-metabolic disturbances promoted by the db/db systemic hyperglycemic-hyperinsulinemic state suppress pituitary gonadotropin release in response to gonadotropin-releasing hormone and gonadal steroid stimulation and results in a hypogonadal-infertility syndrome. Adult female C57BL/KsJ control (+/+ and +/? genotypes) and db/db littermates were monitored for associations in systemic and cellular alterations in luteinizing hormone (LH), follicle-stimulating hormone (FSH), gonadal steroid (binding) levels, and pituitary glucometabolic indices associated with db/db-enhanced lipid imbibition and cytostructural disruption. Obesity, hyperglycemia, and hyperinsulinemia characterized all db/db mutants relative to controls. Serum and pituitary progesterone and estradiol concentrations were suppressed in db/db mutants, in association with serum LH and FSH levels, but not with pituitary LH and FSH concentrations, which were comparable between groups. Pituitary insulin receptor binding and glucose utilization rates were suppressed in db/db groups relative to +/? indices. Structural and cytochemical analysis of anterior (AP), intermediate (IL), and neuro-(NP) hypophyseal lobes demonstrated prominent hypercytolipidemia in db/db mutants relative to controls. Prominent cytolipidemia was localized within well-granulated basophilic gonadotrophs and within IL and NP pituicytes. Vasolipidemia and interstitial cytoadiposity were prominent throughout all db/db pituitary lobes. Thus, disturbances associated with pituitary hypercytolipidemia are functional components of the expressed diabetes-associated hypogonadal syndrome in db/db mutants. Progressive alterations in hypophyseal cytoarchitecture are correlated with suppression of pituitary metabolic and endocrine indices, alterations that contribute to functional disruption of the pituitary-hypogonadal axis in C57BL/KsJ-db/db mice.
 ...
PMID:Structural, metabolic and endocrine analysis of the diabetes (db/db) hypogonadal syndrome: relationship to hypophyseal hypercytolipidemia. 1567 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>