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

In female mammals, reproduction is extremely sensitive to the availability of oxidizable metabolic fuels. When food intake is limited or when an inordinate fraction of the available energy is diverted to other uses such as exercise or fattening, reproductive attempts are suspended in favor of processes necessary for individual survival. Both reproductive physiology and sexual behaviors are influenced by food availability. Nutritional effects on reproductive physiology are mediated by changes in the activity of gonadotropin-releasing hormone (GnRH) neurons in the forebrain, whereas the suppression of sexual behaviors appears to be due, at least in part, to decreases in estrogen receptor in the ventromedial hypothalamus. Work using pharmacological inhibitors of glucose and fatty acid oxidation indicates that reproductive physiology and behavior respond to short-term (minute-to-minute or hour-to-hour) changes in metabolic fuel oxidation, rather than to any aspect of body size or composition (e.g., body fat content or fat-to-lean ratio). These metabolic cues seem to be detected in the viscera (most likely in the liver) and in the caudal hindbrain (probably in the area postrema). This metabolic information is then transmitted to the GnRH-secreting or estradiol-binding effector neurons in the forebrain. There is no evidence to date for direct detection of metabolic cues by these forebrain effector neurons. This metabolic fuels hypothesis is consistent with a large body of evidence and seems to account for the infertility that is seen in a number of situations, including famine, eating disorders, excessive exercise, cold exposure, lactation, some types of obesity, and poorly controlled diabetes mellitus.
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PMID:Control of fertility by metabolic cues. 925 2

There exists a growing body of evidence in women that links androgen excess to increases in cardiovascular disease and reproductive site neoplasia. Ten to fifteen percent of women exhibit clinical signs and symptoms of hyperandrogenism wherein more extensive evaluation is warranted. Women with adult acne, android-type obesity, and alopecia often have been treated for cosmetic reasons without regard to the underlying pathophysiology. Adverse changes in insulin resistance, lipids, and apoproteins favor earlier progression of diabetes for some patients and an unfavorable cardiovascular risk profile for most. Patients with polycystic ovarian syndrome (PCOS) often present to different health providers with different complaints that include excessive facial hair, obesity, hypertension, impaired glucose tolerance, dysfunctional uterine bleeding, or infertility. First-line treatment options, after excluding ovarian or adrenal tumors, include use of non-androgenic OCs until pregnancy is desired. Early identification of patients allows for use of risk-reduction strategies, which may affect clinical outcomes.
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PMID:Androgen excess in women. 882 97

The high prevalence of obesity and its well documented association with the cardiovascular risk factors diabetes mellitus, dyslipidemia and hypertension represents a major problem for the general health status of industrialized societies. Although numerous studies have shown that genetic factors have a major influence on the regulation of energy homeostasis and the susceptibility to obesity, the genes and predisposing mutations involved are insufficiently understood. Among several known rodent models of obesity due to single gene mutations, mice homozygous for the obese (ob) gene exhibit massive early-onset obesity, hyperphagia, non-insulin-dependent diabetes mellitus, defective thermoregulation and infertility. Recently the ob gene was identified by positional cloning and shown to be mutated in ob/ob mice. Leptin, the product of the ob gene, is a 167-amino acid secreted protein that is synthesized exclusively in adipose tissue. With the exception of ob/ob mice, circulating plasma leptin is elevated in obesity. Administration of recombinant leptin to ob/ob mice reduces fat mass, food intake, hyperglycemia and hyperinsulinemia. The various effects of the hormone are mediated by leptin receptors expressed at high levels in the hypothalamus, but also in several other non-neuronal tissues. A mutation in the leptin receptor gene is responsible for the obese phenotype of db/db mice. Plasma leptin in humans is positively correlated with body fat mass, suggesting that leptin resistance rather than leptin deficiency is a common feature of human obesity. This review briefly summarizes the current status of the rapidly growing evidence that leptin plays an important role in the regulation of body weight and fat deposition.
Exp Clin Endocrinol Diabetes 1996
PMID:Regulation of energy balance by leptin. 888 45

Over a nine-year period extending from January 1986 to December 1994, eighteen cases of pernicious anemia occurring in Arabs were diagnosed at King Khalid University Hospital in Riyadh. There were 12 Saudi Arab patients and 6 non-Saudi Arabs. There were 11 males and 7 females. The mean age at presentation was 51 years. The presenting symptoms, laboratory features and the disease pattern were similar to those described in northern European patients in most respects with two possible exceptions. First, the mean age at presentation was lower and second, there was a higher frequency of the antibody to intrinsic factor than previously described in northern Europeans. Both differences have been previously noted in Blacks. Associated autoimmune diseases were identified in two patients, one of whom had diabetes mellitus and vitiligo while the other had a remote history of Graves' disease. One young female patient with primary infertility successfully conceived shortly following the initiation of appropriate cyanocobalamin therapy.
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PMID:Pernicious anemia in Arabs. 893 50

Temporal coordination of biologic processes with an approximately 24-h cycle (circadian) is common throughout the animal and plant kingdom and even in some prokaryotic organisms. In all organisms studied, the capability to keep biologic time is an inherited characteristic located intracellularly. These biological clocks anticipate and get the organism ready for regular environmental changes. This indicates both the ubiquity and the weight of the selective environmental pressure to keep time accurately. Several molecular strategies for biologic time keeping have apparently arisen independently several times throughout evolution. The anatomic, biochemical, and molecular mechanisms of the clock are in the process of being defined. This temporal organization at the cellular, organ, and organismic levels results in predictable differences in the capacity of plants, animals, and human beings to respond to therapeutic interventions administered at different times throughout important biologic cycles (e.g., circadian timed therapy). In the treatment of the cancer bearing host, circadian timing of surgery, anticancer drugs, radiation therapy, and biologic agents can result in improved toxicity profiles, enhanced tumor control, and improved host survival. The routine clinical application of such principles is facilitated by the availability of programmable drug delivery devices. Rhythm frequency ranges other than 24-h (e.g., low frequency: menstrual; high frequency: 10 to 120 min) may also be important to understanding health and disease and to designing successful therapy in diseases as diverse as cancer, infertility, and diabetes.
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PMID:Circadian rhythms and cancer chemotherapy. 895 71

It is now known that human exposure to certain chemicals e.g. benzene, halocarbons, ketones, nitrosamines, etc. can result in adverse health effects that are often not easily recognised as manifestations of chemical toxicity. These are inflammatory states, such as hepatitis, nephritis, scleroderma, and lupus, due to production of reactive oxygen species (ROS) through activation of cytochrome P4502E1 by the chemical, or by metabolism of the chemical to reactive intermediates and neoantigens which initiate immunotoxic effects. Intracellular glutathione (GSH), vitamins C, E and A protect against this ROS toxicity and inflammation; fasting and consumption of alcohol exacerbate it. Chronic inflammatory states may subsequently develop, including rheumatoid disease, atherosclerosis, diabetes, infertility and birth defects, multiple system organ failure (MSOF), Alzheimer's disease, and cancer.
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PMID:Chemical-induced inflammation and inflammatory diseases. 897 63

X-chromosomal recessive bulbospinal neuronopathy (X-BNS, Kennedy's disease) is an important differential diagnosis of amyotrophic lateral sclerosis. We present the data of ten own patients along with a review of the literature on this uncommon disease which is caused by an expanded CAG-repeat in the androgen receptor gene. This mutation probably affects the transcription regulating activity of the androgen receptor in neurons. Signs and symptoms of X-BSN can be derived from partial insensitivity for androgens and a mixed, mainly motor neuronopathy. The clinical diagnosis is based on: 1. lower motor neuron weakness of bulbar and proximal limb muscles with onset in the third to fifth decade, 2. cramps and pronounced fasciculations, particularly of facial muscles, 3. postural tremor, 4. diminished or absent sensory action potentials inspite of only minor sensory impairment, 5. gynecomastia, and 6. infertility, diabetes mellitus and hyperlipoproteinemia in a minority of cases. Unlike amyotrophic lateral sclerosis, disease progression is slow with barely shortened life expectancy, which should be stressed in patient counselling. Causal treatment is as yet unavailable but several aspects of palliative medicine should be considered.
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PMID:[X chromosomal bulbospinal neuropathy (X-BSN, Kennedy syndrome): an illness with repetitive triplet sequences. Case report, differential diagnosis and molecular genetics aspects]. 908 89

Cpefat mice carry a mutation in the carboxypeptidase E/H gene which encodes an exopeptidase that removes C-terminal basic residues from endoproteolytically cleaved hormone intermediates. These mice have endocrine disorders including obesity, infertility, and hyperproinsulinemia-diabetes syndrome, but the etiology remains an enigma. Because studies have identified membrane carboxypeptidase E as a sorting receptor for targeting prohormones to the regulated secretory pathway for processing and secretion, the intracellular routing and secretion of pro-opiomelanocortin/adrenocorticotropin and growth hormone from anterior pituitary cells were investigated in Cpefat mice. In Cpefat mice, pro-opiomelanocortin was accumulated 24-fold above normal animals in the pituitary and it was poorly processed to adrenocorticotropin. Furthermore, pro-opiomelanocortin was secreted constitutively at high levels, showing no response to stimulation by corticotropin-releasing hormone. Similarly, growth hormone release was constitutive and did not respond to high K+ stimulation. Both pro-opiomelanocortin and growth hormone levels were elevated in the circulation of Cpefat mice versus normal mice. These data provide evidence that the lack of carboxypeptidase E, the sorting receptor, results in the intracellular misrouting and secretion of pro-opiomelanocortin and growth hormone via the constitutive pathway in the pituitary of Cpefat mice.
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PMID:Intracellular misrouting and abnormal secretion of adrenocorticotropin and growth hormone in cpefat mice associated with a carboxypeptidase E mutation. 914 34

Mutations in the obese gene (OB) or in the gene encoding the OB receptor(OB-R) result in obesity, infertility and diabetes in a variety of mouse phenotypes. The demonstration that OB protein (also known as leptin) can normalize body weight in ob/ob mice has generated enormous interest. Most human obesity does not appear to result from a mutant form of leptin: rather, serum leptin concentrations are increased and there is an apparent inability to transport it to the central nervous system (CNS). Injection of leptin into the CNS of overfed rodents resistant to peripheral administration was found to induce biological activity. Consequently, for the leptin to act as a weight-lowering hormone in human obesity, it appears that appropriate concentrations must be present in the CNS. This places a premium on understanding the structure of the hormone in order to design more potent and selective agonists. Here we report the crystal structure at 2.4A resolution of a human mutant OB protein (leptin-E100) that has comparable biological activity to wild type but which crystallizes more readily. The structure reveals a four-helix bundle similar to that of the long-chain helical cytokine family.
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PMID:Crystal structure of the obese protein leptin-E100. 914 95

Patients suffering from diabetes mellitus often develop reproductive dysfunction including anovulation, infertility and disrupted pregnancy. The biochemical basis of these phenomena is yet to be provided. The current study utilizes a neuroendocrine paradigm involving an in vitro microdissection technique in conjunction with jugular catheterization to examined the proestrus dynamics of norepinephrine (NE) and the preovulatory luteinizing hormone (LH) surge in streptozotocin (STZ) treated female rats, an animal model for insulin dependent diabetes mellitus. Radioimmunoassays revealed that in control subjects LH was at basal level during the morning of proestrus (900-1200 h); the first significant increase in the level of this pituitary hormone occurred at 1400-1500 h. A maximum peak concentration of LH was attained at 1700 h. In contrast, plasma levels of LH in diabetic subjects showed the first significant increase at 1500 h and peaked at 2000 h. The peak of the LH curve in diabetic rats was reduced by about 65% with a 3 h shift to the right. Alpha-methyl-p-tyrosine-induced blockade of newly synthesized NE-based assay showed that NE turnover rates in several hypothalamic nuclei (e.g. medial preoptic nucleus, MPN; median eminence, ME; suprachiasmatic nucleus, SCN; arcuate nucleus, AN) of control subjects were at basal level during the morning of proestrus (0900-1100 h). However, they increased by the 1200-1400 h interval and remained elevated during the 1500-1700 h. This time dependent increase in hypothalamic NE turnover rates during proestrus was not observed in the STZ diabetic rats. Most of the above metabolic derangements were partially reversed following the institution of insulin replacement therapy. Overall, our data support the concept that the endocrine abnormalities (e.g. infertility, delayed preovulatory LH surge) in diabetes are due, at least in part, to a functional deficit in noradrenergic neurons within the hypothalamus.
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PMID:The role of catecholamines in the etiology of infertility in diabetes mellitus. 920 Jun 71


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