Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucagon (1-1.5 mg) was administrated iv as a bolus dose to healthy individuals (n = 7), patients with GH deficiency (n = 14), and patients with insulin-dependent diabetes mellitus (IDDM; n = 6). Thereafter, blood samples for determination of serum glucose, insulin, insulin-like growth factor-binding protein-1 (IGFBP-1), GH, and insulin-like growth factor-I (IGF-I) concentrations were collected for 180 min. IGFBP-1 concentrations increased significantly in response to glucagon, with maximal values observed at 90 min [in healthy subjects from 36 +/- 6 to 58 +/- 10 micrograms/L (P < 0.05), in GH-deficient patients from 36 +/- 4 to 54 +/- 6 micrograms/L (P < 0.001), and in IDDM patients from 115 +/- 18 to 167 +/- 27 micrograms/L (P < 0.05)]. The IGFBP-1 elevation was delayed in relation to the glucagon-induced increase in glucose and insulin concentrations. When the groups were combined, the individual IGFBP-1 peak value observed at 90 min was inversely correlated to the individual peak value of insulin observed at 15-30 min (r = -0.743; P < 0.001). In GH-deficient patients, serum GH concentrations remained undetectable (< 0.2 micrograms/L), and IGF-I concentrations were unchanged after the glucagon injection. In healthy subjects and IDDM patients, mean GH levels did not change significantly, whereas mean IGF-I concentrations decreased slightly at 30 min. In conclusion, glucagon increased serum IGFBP-1 concentrations in spite of increases in glucose and insulin. These results suggest that glucagon is a stimulator of IGFBP-1.
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PMID:Glucagon stimulates insulin-like growth factor binding protein-1 secretion in healthy subjects, patients with pituitary insufficiency, and patients with insulin-dependent diabetes mellitus. 752 39

Insulin-dependent diabetes mellitus (IDDM) during puberty is associated with a reduction in circulating concentrations of insulin-like growth factor-I (IGF-I) and low IGF bioactivity. Altered levels of the IGF-binding proteins (IGFBPs), including low IGFBP-3 and elevated IGFBP-1, have also been described. These abnormalities have been linked to poor growth and deteriorating blood glucose control. We have therefore examined the effects of recombinant human IGF-I (rhIGF-I) administration on the levels of IGF-I, IGF-II, IGFBP-1, IGFBP-3 and IGF bioactivity in a group of 9 late-pubertal adolescents with IDDM. This was a double-blind placebo controlled study with each individual admitted on two occasions when either rhIGF-I (40 micrograms/kg) or placebo was administered by subcutaneous injection in the thigh at 1800 h. Blood samples were then taken for the subsequent 22 h. The half-life of administered rhIGF-I (12.1-22.2 h) was similar to that previously described in normal subjects. There was a small increase in IGFBP-3 concentrations overnight following rhIGF-I administration when compared to placebo, whereas the levels of IGF-II decreased. Under strict euglycaemic conditions, the relationship between insulin and IGFBP-I did not appear to be affected by rhIGF-I administration although the levels of IGFBP-1 tended to be higher overnight. IGF bioactivity was low during the placebo study, and although within the normal adult range following administration of IGF-I, was still relatively low for adolescents in late puberty.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of recombinant human insulin-like growth factor-I (IGF-I) administration on the levels of IGF-I, IGF-II and IGF-binding proteins in adolescents with insulin-dependent diabetes mellitus. 752 62

The salivary glands of mammals synthesize and secrete a number of peptide growth factors that play important roles in cell/tissue homeostasis and embryonic development. Using a radioimmunoassay, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) were detected in saliva from mice. Unlike epidermal growth factor (EGF), there was no sexual dimorphism in the concentrations of the insulin growth factor family. Immunohistochemical localization of IGF-I and IGF-II was confined to the duct cells of both the parotid and the submandibular glands. Reverse transcriptase-polymerase chain reaction amplification of total RNA from parotid and submandibular glands confirmed the presence of all three hormone/growth factor mRNAs in both glands. The levels of insulin and IGF-I were higher in saliva from an animal model for autoimmune type 1 diabetes, the non-obese diabetic (NOD) mouse, than in a second inbred strain, BALB/c. In contrast, the IGF-II levels were decreased relative to the BALB/c strain. With the onset of diabetes in NOD mice, insulin levels declined, while IGF-I and IGF-II levels showed trends toward lower levels of these growth factors when compared with non-diabetic animals. These changes were reflected in the concentrations from parotid and submandibular gland cell lysates.
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PMID:Detection of insulin and insulin-like growth factors I and II in saliva and potential synthesis in the salivary glands of mice. Effects of type 1 diabetes mellitus. 776 95

We evaluated levels of insulin-like growth factor-I and interleukin-1 alpha and beta in patients with pancreatic cancer; the role of these substances in tumor spread and in hyperglycemia was also investigated. Thirty pancreatic cancer patients (21 with hyperglycemia) were compared with others with diseases causing hyperglycemia [liver cirrhosis (14 cases, 12 with hyperglycemia), chronic pancreatitis (20 cases, 12 with hyperglycemia), type I diabetes mellitus (13 cases, all hyperglycemic)]. Insulin-like growth factor-I was significantly reduced in patients with liver cirrhosis, probably due to a reduced hepatic capacity for synthesis. It was increased in 6 of 30 pancreatic cancer patients; in these subjects it was correlated with alanine aminotransferase and C-peptide, but not with tumor diameter or the presence of metastases. Interleukin-1 alpha and beta were both elevated in pancreatic cancer patients. The former was high, while the latter was low when liver metastases were present. Neither was related to glucose or C-peptide levels. In summary, insulin-like growth factor-I levels are increased in some pancreatic cancer patients but this does not seem to favor tumor spread; however IGF-I could be involved influencing glucose homeostasis. Interleukin-1 alpha increased, while interleukin-1 beta decreased in pancreatic cancer patients with metastases, suggesting a different involvement of these two substances in pancreatic cancer spread.
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PMID:Insulin-like growth factor-I, interleukin-1 alpha and beta in pancreatic cancer: role in tumor invasiveness and associated diabetes. 778 9

We have previously demonstrated weekly iv insulin-like growth factor-I (IGF-I; 500 micrograms/kg) bolus therapy to be effective in inducing sustained insulin sensitivity in a patient with type I diabetes mellitus and massive insulin resistance. The present study was undertaken to determine the efficacy of daily sc IGF-I in the treatment of two severely insulin-resistant type I diabetic patients (requiring in excess of 3500 U insulin/day) compared to weekly iv IGF-I therapy. Prolonged insulin sensitivity was achieved in both patients after weekly 500 micrograms/kg iv bolus infusions of IGF-I, with sc insulin requirements falling to approximately 1 U/kg.day. Smaller iv doses (250 micrograms/kg) of IGF-I were ineffective in acutely lowering serum glucose or inducing sustained insulin sensitivity. However, even this smaller IGF-I dose resulted in acute symptomatic hypophosphatemia, which could be prevented by coadministration of potassium phosphate. With sc administered IGF-I (up to 10 mg twice daily), insulin appeared to control patient glucose concentrations, but severe insulin resistance returned within 72 h of discontinuing IGF-I therapy. IGF-I dosing was decreased to the lowest concentration that maintained euglycemia (7.5 mg in the morning and 2.5 mg in the evening). However, severe arthropathy in both patients and neurological symptoms including multiple cranial nerve palsies in one patient were associated with chronic therapy. We conclude that both iv and sc administered IGF-I can precipitate acute symptomatic hypophosphatemia. Chronic low dose sc therapy may be associated with severe neuropathy and arthropathy, and does not induce the sustained insulin sensitivity associated with high dose intermittent bolus IGF-I therapy.
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PMID:High dose intravenous, but not low dose subcutaneous, insulin-like growth factor-I therapy induces sustained insulin sensitivity in severely resistant type I diabetes mellitus. 804 59

Insulin-dependent diabetes mellitus (IDDM), when untreated or poorly controlled in mammals, results in growth retardation. To determine whether the same relationship exists in an ectothermic vertebrate, IDDM-like symptoms were induced in a teleost fish, the goby Gillichthys mirabilis, by surgical removal of its pancreatic endocrine (islet) organ. Isletectomized (Ix) gobies lost body weight, their skeletal growth was retarded, as measured by changes in body length, and they exhibited a 50% reduction in cartilage 35SO4 incorporation in vitro, consistent with changes that occur in mammals with IDDM. Injections of bovine insulin into the Ix fish restored body growth parameters to control levels and stimulated cartilage 35SO4 incorporation in a dose-related manner. In contrast to mammals with IDDM, which are resistant to GH action, injection of teleost GH stimulated cartilage 35SO4 incorporation in the Ix fish. Furthermore, whereas cartilage from rats with IDDM is resistant to stimulation by insulin-like growth factor-I (IGF-I) in vitro, cartilage explants from the Ix fish were highly responsive to recombinant bovine IGF-I, exhibiting a dose-dependent stimulation of 35SO4 incorporation. As far as we are aware, these results represent the first demonstration of diabetic growth inhibition in an ectothermic vertebrate. This inhibition is similar to that which occurs in mammals with IDDM in some respects, but is different in others, as the diabetic fish did not develop resistance to growth stimulation by either GH or IGF-I. While these results support a role for insulin in maintaining the GH-IGF-I-growth axis in this ectothermic vertebrate, there may be important differences in the role of insulin in the promotion of anabolic processes.
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PMID:Experimental diabetes mellitus in a teleost fish. II. Roles of insulin, growth hormone (GH), insulin-like growth factor-I, and hepatic GH receptors in diabetic growth inhibition in the goby, Gillichthys mirabilis. 850 69

Insulin resistance characterizes non-insulin dependent diabetes (NIDDM). Insulin resistance may coexist in clinical syndromes with hyperestrogenism and hyperandrogenism, suggesting that the ovary may be sensitive to effects of insulin. In addition, insulin-like growth factor-I receptors, which are capable of binding insulin, have been identified in ovarian cancer tissue and are proposed to regulate cell growth. We evaluated the association between a history of diabetes mellitus and ovarian cancer in a case-control study in seven counties in Washington and in Utah (United States) during the years 1975-87. Cases included women newly diagnosed with ovarian cancer over a five-year period who were identified through population-based cancer reporting. Controls similar to cases with regard to age and county of residence were identified via household surveys or random digit dialing. The study included 595 cases and 1,587 controls. Twenty-seven cases (4.5 percent) and 72 controls (4.5 percent) reported a history of diabetes. Logistic regression analysis of the association between diabetes and ovarian cancer controlling for age, body mass index, and race resulted in an odds ratio (OR) of 0.9 (95 percent confidence interval [CI] = 0.6-1.5). The OR was not changed with further controlling for prior oral contraceptive use or prior pregnancy. None of the 20 women with nonepithelial tumors (15 of which were stromal tumors) had a history of diabetes (upper CI = 4.0). These results, together with findings of two earlier cohort studies, do not support the hypothesis that diabetes is a risk factor for epithelial ovarian cancer.
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PMID:Is diabetes mellitus a risk factor for ovarian cancer? A case-control study in Utah and Washington (United States). 881 36

To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) has direct effects on the insulin requirement to maintain euglycemia independent of the growth hormone (GH) level, nine subjects with insulin-dependent diabetes mellitus ([IDDM] seven females; median (range) age, duration of diabetes, and hemoglobin A1C [HbA1C], 16.9 (12.5 to 21.9) years, 11.8 (4.6 to 16.8) years, and 9.8% (7.9% to 14.1%), respectively) underwent two euglycemic studies (6:00 PM to 8:00 AM) after double-blind subcutaneous administration of rhIGF-I/placebo (40 microg/kg). Octreotide infusion (300 ng/kg/h) suppressed endogenous GH, and three identical discrete GH pulses were infused on both nights. Variable-rate insulin infusion maintained euglycemia. Samples were taken every 15 minutes (glucose and GH), 30 minutes (insulin and intermediate metabolites), and 60 minutes (IGF-I and nonesterified fatty acids [NEFA]). Variables were analyzed during the steady-state period of euglycemia (4:00 to 8:00 AM). Data are expressed as the mean +/- SEM. The insulin infusion rate and free-insulin level were both significantly reduced after rhIGF-I administration (0.13 +/- 0.03 v placebo 0.23 +/- 0.05 mU/kg/min, P = .04, and 8.4 +/- 1.3 v placebo 12.1 +/- 1.4 mU/L, P = .03, respectively). GH pulse-related changes in the insulin requirement observed after placebo were not present after rhIGF-I. Glucagon levels were equally suppressed on both nights. Insulin clearance was not altered after rhIGF-I administration. NEFA and ketone levels also were not different on the 2 nights. In conclusion, in adolescents and young adults with diabetes, rhIGF-I administration directly affected insulin requirements independent of GH levels, but had no effect on fatty acid or ketone levels. This difference is related to the abolition of changes in the insulin requirement after GH pulses, and would suggest a complex interaction between GH and IGF-I on insulin action.
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PMID:Recombinant human insulin-like growth factor-I abolishes changes in insulin requirements consequent upon growth hormone pulsatility in young adults with type I diabetes mellitus. 944 Apr 74

Apoptosis or programmed cell death is a physiological form of cell death that occurs in embryonic development and during involution of organs. It is characterized by distinct biochemical and morphological changes such as DNA fragmentation, plasma membrane blebbing and cell volume shrinkage. Many hormones, cytokines and growth factors are known to act as general and/or tissue-specific survival factors preventing the onset of apoptosis. In addition, many hormones and growth factors are also capable of inducing or facilitating programmed cell death under physiological or pathological conditions, or both. Steroid hormones are potent regulators of apoptosis in steroid-dependent cell types and tissues such as the mammary gland, the prostate, the ovary and the testis. Growth factors such as epidermal growth factor, nerve growth factor, platelet-derived growth factor (PDGF) and insulin-like growth factor-I act as survival factors and inhibit apoptosis in a number of cell types such as haematopoietic cells, preovulatory follicles, the mammary gland, phaeochromocytoma cells and neurones. Conversely, apoptosis modulates the functioning and the functional integrity of many endocrine glands and of many cells that are capable of synthesizing and secreting hormones. In addition, exaggeration of the primarily natural process of apoptosis has a key role in the pathogenesis of diseases involving endocrine tissues. Most importantly, in autoimmune diseases such as autoimmune thyroid disease and type 1 diabetes mellitus, new data suggest that the immune system itself may not carry the final act of organ injury: rather, the target cells (i.e. thyrocytes and beta cells of the islets) commit suicide through apoptosis. The understanding of how hormones influence programmed cell death and, conversely, of how apoptosis affects endocrine glands, is central to further design strategies to prevent and treat diseases that affect endocrine tissues. This short review summarizes the available evidence showing where and how hormones control apoptosis and where and how programmed cell death exerts modulating effects upon hormonally active tissues.
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PMID:Hormonal control of programmed cell death/apoptosis. 962 57

Human milk lipids contain preformed LCPUFA in considerable amounts, which serve as precursors for the formation of prostaglandins, prostacyclins, and other lipid mediators, as well as essential components in membrane-rich tissues (such as the brain and the retina), thus affecting functional outcomes. Besides a balanced nutrient composition and a number of conditionally essential nutrients, human milk provides different types and classes of bioactive factors, such as enzymes, hormones, and growth factors, many of which appear to have a role in supporting infantile growth and development. The bioactive agents include antimicrobial factors (e.g., secretory IgA, oligosaccharides, FA); anti-inflammatory agents; transporters (e.g., lactoferrin); and digestive enzymes (e.g., BSSL). Several nonpeptide hormones (thyroid hormones, cortisol, progesterone, pregnanediol, estrogens, and artificial contraceptive) and peptide hormones and growth factors (erythropoietin, hHG, gonadotropin-releasing hormone, epidermal growth factor insulin, insulin-like growth factor-I, nerve growth factor, transforming growth factor-alpha, gastrointestinal regulatory peptides and thyroid-parathyroid hormones) have been isolated and quantitated in human milk. Some of these components are also involved in the maturation of the gastrointestinal tract of the infant. In addition to the passive benefits provided by human milk, several data support the hypothesis that breastfeeding promotes the development of the infant's own immune system, which might confer long-term benefits for the newborn infant. The risk of IDDM, Crohn's disease, and atopic disease is lower in individuals who had been breastfed during infancy. Areas of major interest in human milk research include the study of human milk synthesis and the contributions of dietary composition and maternal metabolism to human milk composition, infantile utilization of human milk components, and the study of bioactive components, such as oligosaccharides, proteins and peptides, and lipids and their in vivo fate and biologic effects in the recipient infant.
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PMID:Nutritional and biochemical properties of human milk: II. Lipids, micronutrients, and bioactive factors. 1039 91


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