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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta endorphin (beta-EP) is an important modulator of central pain pathways. To examine whether changes in central production of beta-EP contribute to the pathogenesis of diabetic neuropathic pain, we compared the cerebrospinal fluid (CSF) levels of beta-EP and its precursor proopiomelanocortin (POMC) between 15 diabetic patients with chronic painful diabetic polyneuropathy, eight patients with severe painless diabetic neuropathy, and ten nondiabetic controls. Both peptides were measured by specific monoclonal antibody-based two-site immunoradiometric assays (IRMAs). In the diabetic patients with painful neuropathy, mean +/- SD CSF beta-EP concentrations (5.7 +/- 2.2 pmol/L) were comparable to those of the diabetic patients with painless neuropathy (6.0 +/- 2.3 pmol/L) and did not correlate with the severity of neuropathic pain. CSF beta-EP, but not POMC, concentrations were lower in the diabetic neuropathic patients overall (5.8 +/- 1.9 pmol/L) compared to the control subjects (7.6 +/- 2.2 pmol/L) (p < 0.05). CSF POMC showed no intergroup differences. However, POMC levels were 80-fold higher than those of beta-EP and should always be considered when interpreting immunoreactive beta-EP or other derivative peptide levels in CSF. We conclude that CSF beta-EP levels appear to be reduced in diabetic polyneuropathy but they do not relate to the presence of neuropathic pain. This might explain why opioid analgesics are of little, if any, help in alleviating diabetic neuropathic pain.
J Diabetes Complications
PMID:Cerebrospinal fluid levels of beta endorphin in painful and painless diabetic polyneuropathy. 759 54

In the horse, adenomata of the pairs intermedia of the pituitary gland have been associated with the distinct clinical entity of Cushing's disease which arises largely as a result of excessive secretion of adrenocorticotropin (ACTH) or other proopiomelanocortin (POMC) peptides. Pars intermedia peptide secretion is under dopaminergic control and compounds such as pergolide or bromocriptine, which are dopamine agonists, can palliate the clinical signs. A variety of endocrinological abnormalities, relevant to both pathogenesis and diagnosis, may be demonstrated in equine Cushing's disease, including hyperadrenocorticism, peripheral insulin resistance and excessive POMC-peptide secretion from the pituitary gland. Preliminary studies on carbohydrate metabolism suggest that quantification of insulin activity may be a useful prognostic index in cases of equine Cushing's disease, and that insulin therapy of secondary diabetes mellitus may be indicated in some cases.
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PMID:Equine Cushing's disease. 848 40

Transgenic nonobese diabetic mice were created in which insulin expression was targeted to proopiomelanocortin-expressing pituitary cells. Proopiomelanocortin-expressing intermediate lobe pituitary cells efficiently secrete fully processed, mature insulin via a regulated secretory pathway, similar to islet beta cells. However, in contrast to the insulin-producing islet beta cells, the insulin-producing intermediate lobe pituitaries are not targeted or destroyed by cells of the immune system. Transplantation of the transgenic intermediate lobe tissues into diabetic nonobese diabetic mice resulted in the restoration of near-normoglycemia and the reversal of diabetic symptoms. The absence of autoimmunity in intermediate lobe pituitary cells engineered to secrete bona fide insulin raises the potential of these cell types for beta-cell replacement therapy for the treatment of insulin-dependent diabetes mellitus.
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PMID:Insulin-secreting non-islet cells are resistant to autoimmune destruction. 871 Sep 16

Melanocortin peptides (adrenocorticotropin (ACTH), alpha-,beta-, and gamma-melanocyte stimulating hormone (MSH), and fragments thereof) derived from proopiomelanocortin (POMC) have a diverse array of biological activities, many of which have yet to be fully elucidated. The recent cloning of a family of five distinct melanocortin receptors through which these peptides act has provided the tools to further our understanding of melanocortin peptide functions. Early work on melanocortin peptides focused on their roles in pigmentation, adrenocortical function, the immune, central and peripheral nervous systems. Although melanocortin peptides have long been known to affect lipolysis, characterisation of the melanocortin receptors has opened up several lines of evidence for important roles in the development of obesity, insulin resistance and type II diabetes. We present here a review of the current evidence for melanocortin peptides playing such a role, and based on this evidence, a model for melanocortin peptides and their receptors in maintaining energy balance.
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PMID:Obesity, diabetes and functions for proopiomelanocortin-derived peptides. 914 88

Streptozotocin-induced diabetes for 4 weeks resulted in a decrease in proopiomelanocortin (POMC) mRNA in both the anterior lobe (AL) and the neuro-intermediate lobe (NIL) of the rat pituitary. The beta-endorphin levels decreased in the NIL but not in the AL. It is concluded that the synthesis of POMC in the pituitary is inhibited in diabetic rats and that there is a decrease in beta-endorphin release from the anterior pituitary.
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PMID:The effect of streptozotocin-diabetes on beta-endorphin level and proopiomelanocortin gene expression in the rat pituitary. 1008 41

Obesity is a significant health problem owing to increased risk for diabetes and cardiovascular disease, and several lines of evidence suggest that alterations in the central melanocortin system might account for some of the genetic contribution to obesity in humans. First, the phenotypic aspects and dominant inheritance of the melanocortin obesity syndromes in the mouse are more like human obesity than other murine obesity syndromes. Second, studies recently published present two rare cases of familial obesity resulting from null alleles of the proopiomelanocortin (POMC) gene, providing the first evidence that the melanocortin pathway in humans subserves the same function in regulation of energy homeostasis as it does in the rodent. Additional studies suggest that heterozygous mutations in the melanocortin 4 receptor might be a common reason for genetic predisposition to obesity in children. Research on the central melanocortin system in rodents suggests that this system might be a fundamental component of the adipostat, the mechanism by which energy stores are held relatively constant, and this hypothesis will be the focus of this review.
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PMID:The Central Melanocortin System and Energy Homeostasis. 1040 94

An accumulation of evidence implicates leptin, insulin, glucocorticoids, proopiomelanocortin (POMC), and neuropeptide Y (NPY) interactions as being integral to metabolic control associated with neuroendocrine-endocrine functioning. Dysfunction of neuroendocrine-endocrine interactions contributes to the metabolic disturbances of diabetes mellitus type 2 (DM-2). Since Zn has a direct impact on the healthy functioning of hormonal and neuropeptide balance, it is possible that altered Zn status and metabolism in DM-2 are involved in some of the metabolic dysfunctions of DM-2.
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PMID:Potential interactions of zinc in the neuroendocrine-endocrine disturbances of diabetes mellitus type 2. 1060 38

A 29-year-old woman was admitted in March 1998 due to high plasma ACTH levels, amenorrhea and uncontrolled diabetes mellitus (DM) which had persisted since 1991. Plasma ACTH levels showed a wide range of changes: they were usually high (59-240 pg/ml), intermittently very high (336-942 pg/ml), and sometimes normal or low. Plasma cortisol levels were usually normal but were sometimes high when the ACTH levels were very high. However, even when the plasma ACTH levels were very high, she did not show any cushingoid features. DM was diagnosed as non-insulin-dependent DM. Plasma ACTH showed an excessive response to CRH, while cortisol showed a delayed response. Plasma cortisol showed a poor response to ACTH-(1-24). ACTH receptor gene analysis revealed no mutations in the ACTH receptor-coding region. MRI showed a nonenhancing mass on the left side of the pituitary. Cavernous sinus sampling showed a very high plasma ACTH level in the left cavernous sinus compared with the levels in the right cavernous sinus and peripheral blood. Sephadex G-75 gel filtration of plasma ACTH immunoreactivity in plasma obtained by cavernous sinus sampling showed mainly high molecular forms of ACTH, probably proopiomelanocortin and ACTH-beta-lipotropin. This case is a very rare form of pituitary adenoma showing intermittent secretion of high molecular ACTH unaccompanied by cushingoid features.
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PMID:Pituitary adenoma showing intermittent secretion of high molecular weight adrenocorticotropin without evidence of Cushing's disease. 1064 Aug 99

Hypothalamic melanocortins are among several neuropeptides strongly implicated in the control of food intake. Agonists for melanocortin 4 (MC-4) receptors such as alpha-melanocyte-stimulating hormone (alpha-MSH), a product of proopiomelanocortin (POMC), reduce food intake, whereas hypothalamic agouti-related protein (AgRP) is a MC-4 receptor antagonist that increases food intake. To investigate whether reduced melanocortin signaling contributes to hyperphagia induced by uncontrolled diabetes, male Sprague-Dawley rats were studied 7 days after administration of streptozotocin (STZ) or vehicle. In addition, we wished to determine the effect of diabetes on muscle uncoupling protein 3 (UCP-3), a potential regulator of muscle energy metabolism. STZ diabetic rats were markedly hyperglycemic (31.3 +/- 1.0 mmol/l; P < 0.005) compared with nondiabetic controls (9.3 +/- 0.2 mmol/l). Insulin treatment partially corrected the hyperglycemia (18.8 +/- 2.5 mol/l; P < 0.005). Plasma leptin was markedly reduced in STZ diabetic rats (0.4 +/- 0.1 ng/ml; P < 0.005) compared with controls (3.0 +/- 0.4 ng/ml), an effect that was also partially reversed by insulin treatment (1.8 +/- 0.3 ng/ml). Untreated diabetic rats were hyperphagic, consuming 40% more food (48 +/- 1 g/day; P < 0.005) than controls (34 +/- 1 g/day). Hyperphagia was prevented by insulin treatment (32 +/- 2 g/day). In untreated diabetic rats, hypothalamic POMC mRNA expression (measured by in situ hybridization) was reduced by 80% (P < 0.005), whereas AgRP mRNA levels were increased by 60% (P < 0.01), suggesting a marked decrease of hypothalamic melanocortin signaling. The change in POMC, but not in AgRP, mRNA levels was partially reversed by insulin treatment. By comparison, the effects of diabetes to increase hypothalamic neuropeptide Y (NPY) expression and to decrease corticotropin-releasing hormone (CRH) expression were normalized by insulin treatment, whereas the expression of mRNA encoding the long form of the leptin receptor in the arcuate nucleus was unaltered by diabetes or insulin treatment. UCP-3 mRNA expression in gastrocnemius muscle from diabetic rats was increased fourfold (P < 0.005), and the increase was prevented by insulin treatment. The effect of uncontrolled diabetes to decrease POMC, while increasing AgRP gene expression, suggests that reduced hypothalamic melanocortin signaling, along with increased NPY and decreased CRH signaling, could contribute to diabetic hyperphagia. These responses, in concert with increased muscle UCP-3 expression, may also contribute to the catabolic effects of uncontrolled diabetes on fuel metabolism in peripheral tissues.
Diabetes 2000 Feb
PMID:Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats. 1086 41

Hypoglycemia reduces sympathoadrenal responses to subsequent hypoglycemic bouts by an unknown mechanism. To assess whether such hypoglycemia-associated autonomic failure is due to actual brain damage, male Sprague-Dawley rats underwent 1-h bouts of insulin-induced (5 U/kg i.v.) hypoglycemia (1.6-2.8 mmol/l) 1 or 3 times on alternate days. Rats remained alert and were rescued with intravenous glucose at 60-80 min. Plasma epinephrine and corticosterone responses were significantly reduced during the second and third bouts. Brains from these rats were processed by the terminal transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) procedure as an index of apoptotic cell death at 24, 48, or 96 h after their first bout. At 48 h, but not 24 h, TUNEL+ cells were consistently seen only in the arcuate nucleus (arcuate hypothalamic nucleus [ARC]). Hypoglycemic rats had 188% more apoptotic ARC cells (1 bout 39+/-5; 3 bouts 37+/-4) than euglycemic controls (13+/-3;P = 0.001). In situ hybridization for neuropeptide Y (NPY) and proopiomelanocortin (POMC) mRNA was performed in sections of ARC containing maximal numbers of apoptotic cells as well as in other fresh frozen brains. After 1 bout, NPY (0.041+/-0.003) and POMC (0.119+/-0.022) mRNA were decreased, respectively, by 52 and 55% vs. controls (NPY 0.076+/-0.007; POMC 0.222+/-0.020; P = 0.01). NPY (0.029+/-0.002) but not POMC (0.093+/-0.013) fell 29% further after a third bout. NPY (r = -0.721; P = 0.001) and POMC (r = -0.756; P = 0.001) mRNA levels correlated negatively with the number of apoptotic ARC cells in the same sections. Thus, non-coma hypoglycemia produces apparent apoptotic cell death with reduced NPY and POMC expression selectively in the ARC. This may contribute to the reduced counterregulatory response following repeated bouts of hypoglycemia.
Diabetes 2000 May
PMID:Presumed apoptosis and reduced arcuate nucleus neuropeptide Y and pro-opiomelanocortin mRNA in non-coma hypoglycemia. 1090 92


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