Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P01275 (glucagon)
26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor II (IGF-II) appears to play an important role during fetal life in cell growth and differentiation in several organs, including the pancreas. In the present study we investigated the cellular localization of IGF-II in human fetal pancreas at 16, 18 and 22 embryonic weeks and compared it with adult pancreas. Single and double immunofluorescence methods were used to study co-localization of IGF-II with the four major islet hormones - insulin, glucagon, somatostatin, pancreatic polypeptide - and with islet amyloid polypeptide (IAPP). Distinct IGF-II immunoreactive (IR) cells were found in the endocrine, but not in the exocrine, pancreas. The intensity of IGF-II immunoreactivity was more pronounced in the fetal than in the adult pancreas. In fetal pancreas IGF-II immunoreactivity was observed in virtually all insulin-IR cells and in subsets of the glucagon, somatostatin and IAPP cells. In the adult pancreas, IGF-II immunoreactivity was found in insulin/IAPP cells only. Our results suggest a broader effect of IGF-II in fetal endocrine pancreatic cells than in the adult.
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PMID:Insulin-like growth factor II in human fetal pancreas and its co-localization with the major islet hormones: comparison with adult pancreas. 1081 Feb 88

We reported a boy with panhypopituitarism after removal of a suprasellar teratoma and pituitary stalk transection at the age of 3 months. His growth was accelerated after 5 years of age without growth hormone (GH) therapy, although he had poor height growth until age 4 under treatment with hydrocortisone, levothyroxine sodium, and desamino-D-arginine vasopressin (DDAVP). Hyperphagia and obesity developed after surgery. Endocrinological examination revealed no GH response to glucagon, low serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein-3 (IGFBP-3). Serum prolactin was normal, but serum insulin was high. Some patients who received an operation for craniopharyngioma were reported to achieve normal growth without GH secretion, but the mechanism is still unknown. High serum levels of prolactin or insulin can be associated with normal IGF in GH deficient patients. This patient had obesity and high serum insulin, which may be related to growth without GH secretion.
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PMID:A boy with normal growth in spite of growth hormone deficiency after resection of a suprasellar teratoma. 1089 Jan 95

Protein kinase B/Akt (PKB/Akt) is activated by phosphatidylinositol 3-kinase (PI 3-K) and is a central mediator of cellular proliferation and protection against apoptosis. Insulin, insulin-like growth factor (IGF-1), and glucagon-like peptide-1 (GLP-1) act as glucose-dependent growth factors for pancreatic beta-cells. We assessed signaling pathways and stimulation patterns of PKB/Akt activation by these ligands in the beta-cell line INS-1. Insulin, IGF-1, and GLP-1 induced distinctive time dependent, dose dependent, and glucose dependent phosphorylation of PKB/Akt. Insulin and IGF-1 stimulated PI 3-K activity was mainly associated with insulin receptor substrate (IRS) isoforms IRS-1 and IRS-2 and less so with the IRS-isoform Grb-2 associated binder-1 (Gab-1). In contrast, GLP-1 induced PI 3-K activity mainly in Gab-1 and also in IRS-2 immunoprecipitates, although in an attenuated kinetic. Thus, activation pathways of PKB/Akt by insulin, IGF-1, and GLP-1 converge at the level of IRS-isoforms and PI 3-K inducing differential activation of PKB/Akt. These data indicate an essential role of PKB/Akt in regulation of beta-cell proliferation.
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PMID:Integrative mitogenic role of protein kinase B/Akt in beta-cells. 1119 29

In earlier studies a high-molecular-weight (HMW) insulin-like growth factor-II (IGF-II) peptide was identified in adult human pancreas and localized to the insulin-producing B-cells. This peptide has now been investigated in neoplastic insulin cells. Forty endocrine pancreatic tumours and 17 pancreatic adenocarcinomas of ductal type were included in the study. All cases were investigated with immunohistochemical techniques using antibodies to IGF-II, insulin, pro-insulin, glucagon, somatostatin, pancreatic polypeptide, gastrin and vasoactive intestinal peptide (VIP). Frozen tissue from nine tumours and two normal pancreatic glands was extracted, gel separated, and quantified using radioimmunoassay. The tumours were also investigated by in situ hybridization. IGF-II-immunoreactive cells were found in nearly all the 18 insulin-producing tumours (16/18), in a minority of the other endocrine tumours, but not in pancreatic adenocarcinomas. All extracts from the endocrine tumours showed varying amounts of IGF-II and had different molecular-weight forms. The immunohistochemical and radioimmunoassay findings are both based on immunological binding and were further confirmed by Northern blot and in situ hybridization. These results show that IGF-II is expressed in insulin-producing tumours as well as in pancreatic tumours producing other peptides, in contrast to normal pancreatic islets where IGF-II is found exclusively in insulin-producing cells.
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PMID:Insulin-like growth factor-II in endocrine pancreatic tumours. Immunohistochemical, biochemical and in situ hybridization findings. 1139 94

Pycnodysostosis is a rare hereditary bone abnormality with an autosomal recessive mode of inheritance. We report the clinical, radiologic, and endocrine status of 8 children with this rare disease. All patients had the characteristic phenotype of the disorder including short stature (8 of 8), increased bone density (7 of 8), separated cranial sutures (8 of 8), large fontanel with delayed closure (8 of 8), obtuse mandibular angle (8 of 8), delayed teeth eruption (8 of 8), enamel hypoplasia (7 of 8), dysplastic acromial ends of the clavicles (6 of 8), frontal bossing (6 of 8), ocular proptosis (8 of 8), and dysplastic nails (8 of 8). Developmental evaluation according to the revised Denever developmental screening showed normal motor, fine motor-adaptive language, and personal social abilities in all the children. All had normal hepatic and renal functions. Serum calcium and phosphorus concentrations were normal. Two children had low serum alkaline phosphatase concentration. Short stature is a characteristic feature of pycnodysostosis. Seven of the 8 children were born short (length standard deviation score [SDS] = -3 to -1.5). Deceleration of linear growth was significant during the first 3 years of life. All the children had height SDS below -3 at the end of their third year of life. Although short stature is a feature of this genetic disorder, defective growth hormone (GH) secretion in response to provocation with clonidine and glucagon was found in 4 of the 8 patients. These 4 patients had pituitary hypoplasia on the magnetic resonance imaging (MRI) of their brain. In addition, 3 of these 4 patients had demyelination of the cerebrum. Patients with pycnodysostosis (n = 8) had low circulating concentrations of insulin-like growth factor-1 (IGF-1) compared with normal age-matched short children with constitutional short stature (CSS). IGF-I increased significantly after injecting GH for 3 days in these patients. Physiologic replacement with GH (18 U/m(2)/week) divided in daily evening doses subcutaneously increased IGF-1 concentration and improved linear growth velocity and height standard deviation scores (HtSDS) in the 4 children with GH deficiency. These data ruled out GH resistance and proved the usefulness of GH therapy in the management of short stature in these patients. In summary, some patients with pycnodysostosis have partial GH deficiency and low IGF-1 concentration. GH therapy markedly increases IGF-I secretion and improves their linear growth. MRI study of the brain including the hypothalamic-pituitary area is recommended in these children because of the high incidence of pituitary hypoplasia and cerebral demyelination.
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PMID:Pycnodysostosis: clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy. 1147 77

To determine if the hormonal effects on insulin-like growth factor binding protein (IGFBP) production differed between granulosa and thecal cells, both cell types were collected and cultured in serum-free medium with various hormone treatments, arranged in three experiments. Following treatment, cells were enumerated and media were collected, concentrated 10-fold and subjected to ligand blotting. Experiment 1 revealed that > or =1.5 x 10(5) viable cells at plating were needed for maximal IGFBP production by granulosa and thecal cells. The major forms of IGFBPs produced were a 27-34-kDa IGFBP (IGFBP-2 and -5), and a 20-22-kDa IGFBP (IGFBP-4) by the granulosa cells and a 40-44-kDa IGFBP (IGFBP-3), 34-kDa IGFBP (IGFBP-2), 27-29-kDa IGFBP (IGFBP-5) and a 20-22-kDa IGFBP (IGFBP-4) by the thecal cells. In Experiment 2A, insulin stimulated production of IGFBP-5 by thecal cells, and basic fibroblast growth factor (bFGF) inhibited the insulin-induced increase in IGFBP-5 production; epidermal growth factor (EGF) and luteinizing hormone were without effect. The small amounts of IGFBP-2 and -3 produced by thecal cells of Experiment 2A were not affected by treatment. Production of IGFBP-2/-5 by granulosa cells in Experiment 2B was inhibited by insulin, with EGF and bFGF further enhancing insulin's inhibitory effect; follicle-stimulating hormone was without effect. In Experiment 3A, insulin enhanced production of IGFBP-5 by thecal cells whereas glucagon blocked insulin's stimulatory effect. In contrast, insulin or glucagon alone had no effect on production of the IGFBP-4 by thecal cells but when combined inhibited IGFBP-4 production. The small amounts of IGFBP-2 and -3 produced by thecal cells of Experiment 3A were not affected by treatment. In Experiment 3B, production of IGFBP-2/-5 by granulosa cells was attenuated in the presence of cortisol with or without insulin and insulin plus glucagon; glucagon and cortisol decreased production of IGFBP-4 by granulosa cells. These results suggest that production of IGFBP-2, -4, and -5 by granulosa and thecal cells are differentially affected by hormonal stimuli, and that IGFBP-3 is more consistently produced by thecal cells than granulosa cells of cattle although its production was not hormonally regulated.
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PMID:Hormonal control of ovarian cell production of insulin-like growth factor binding proteins. 1150 Feb 40

A weight-reducing effect of metformin has been demonstrated in obese subjects with and without diabetes. The mechanisms of this action are unclear, which may be partly due to the fact that in obese and diabetic patients the substance's effects result from a complex interaction with the distinct endocrine and metabolic disturbances in these patients. To dissociate primary from secondary action of metformin, we examined effects of the substance in normal-weight healthy subjects. Fifteen normal-weight men were treated with metformin (850 mg twice daily) or placebo for a 15-day period in a double-blind, placebo-controlled, cross-over study. Anthropometric, psychologic, cardiovascular, endocrine, and metabolic parameters were assessed before and at the end of the treatment period. Metformin did not affect body weight (P =.838) and body fat mass (P =.916). Yet, serum leptin concentration was distinctly reduced after metformin (P <.001). Also, metformin reduced the concentration of plasma glucose (P =.011), serum insulin (P=.044), and serum insulin-like growth factor -1 (IGF-1) (P=.013), while it increased serum glucagon concentration (P <.001). There were no effects of metformin on feelings of hunger, blood pressure, heart rate, resting energy expenditure, the respiratory quotient, free fatty acids, beta-hydroxybutyrate, glycerol, triglycerides, cholesterol, and uric acid (all P >.1). Data indicate that metformin decreases the serum leptin concentration even without affecting body weight and body composition in normal-weight men.
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PMID:Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal-weight healthy men. 1191 66

The aim of this present investigation was to study the relationship between the reduction in insulin sensitivity accompanying 5 days of treatment with growth hormone (GH; 0.05 mg.24 h(-1).kg(-1)) and intracellular substrate oxidation rates in six healthy subjects, while maintaining glucose flux by a constant glucose infusion and adjusting insulin infusion rates to achieve normoglycaemia (feedback clamp). Protein synthesis rates in skeletal muscle (flooding dose of L-[(2)H(5)]phenylalanine) were determined under these conditions. We also compared changes in insulin sensitivity after GH treatment with simultaneous changes in energy requirements, protein synthesis rates, nitrogen balance, 3-methylhistidine excretion in urine, body composition and the hormonal milieu. After GH treatment, 70% more insulin was required to maintain normoglycaemia (P<0.01). The ratio between glucose infusion rate and serum insulin levels decreased by 34% at the two levels of glucose infusion tested (P<0.05). Basal levels of C-peptide, insulin-like growth factor (IGF)-I and IGF-binding protein-3 increased almost 2-fold, while levels of glucose, insulin, glucagon, GH and IGF-binding protein-1 remained unchanged. Non-esterified fatty acid levels decreased (P<0.05). In addition, 24 h urinary nitrogen excretion decreased by 26% (P<0.01) after GH treatment, while skeletal muscle protein synthesis and 3-methylhistidine excretion in urine remained unchanged. Energy expenditure increased by 5% (P<0.05) after treatment, whereas fat and carbohydrate oxidation were unaltered. In conclusion, when glucose flux was normalized by compensatory hyperinsulinaemia under conditions of GH-induced insulin resistance, intracellular rates of oxidation of glucose and fat remained unchanged. The nitrogen retention accompanying GH treatment seems to be due largely to improved nitrogen balance in non-muscle tissue.
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PMID:Glucose flux is normalized by compensatory hyperinsulinaemia in growth hormone-induced insulin resistance in healthy subjects, while skeletal muscle protein synthesis remains unchanged. 1191 8

The effect of intestinal glucose supply on whole body rate of glucose appearance (WBGRa) and mammary utilization of glucose was studied in four lactating dairy cows. Glucose (0, 443, 963 and 2398 g/d) was continuously infused in the duodenum over 14-d periods using a Latin square design. A grass silage-based diet was formulated so that treatments were isoenergetic and isonitrogenous and contained 100 and 110% of energy and protein requirements according to INRA (1989). The WBGRa was measured by the [6,6-(2)H2]glucose dilution technique, and mammary glucose balance by arteriovenous differences and blood flow measurements. Duodenal glucose infusion increased arterial glucose concentrations linearly, whereas arterial concentrations of insulin, growth hormone, and glucagon were not changed. The WBGRa increased linearly with increasing glucose loads. The increase represented 42% of the intestinal glucose supplement. Mammary blood flow dramatically increased (up to 45%) and was associated with a significant increase of arterial insulin-like growth factor-1 concentrations. Mammary gland rate of glucose disappearance ([6,6-(2)H2]glucose measurement) increased linearly, whereas net mammary balance of glucose, lactose, and milk yields increased quadratically. Net mammary balance of glucose accounted for 60% of WBGRa, except for the greatest dose (47.6%). The decrease in milk yield with 2398 g/d of glucose may be explained by an imbalance in intracellular intermediate concentrations. The milk ratio of glucose-1-phosphate to glucose-6-phosphate decreased significantly at the greatest infusion of glucose. In conclusion, exogenous glucose supply to a grass silage-based diet increased WBGRa, mammary utilization of glucose and milk synthesis.
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PMID:Duodenal glucose increases glucose fluxes and lactose synthesis in grass silage-fed dairy cows. 1194 64

The subtilisin-like proprotein convertases PC1/3 (SPC3) and PC2 (SPC2) are believed to be the major endoproteolytic processing enzymes of the regulated secretory pathway. They are expressed together or separately in neuroendocrine cells throughout the brain and dispersed endocrine system in both vertebrates and invertebrates. Disruption of the gene-encoding mouse PC1/3 has now been accomplished and results in a syndrome of severe postnatal growth impairment and multiple defects in processing many hormone precursors, including hypothalamic growth hormone-releasing hormone (GHRH), pituitary proopiomelanocortin to adrenocorticotropic hormone, islet proinsulin to insulin and intestinal proglucagon to glucagon-like peptide-1 and -2. Mice lacking PC1/3 are normal at birth, but fail to grow normally and are about 60% of normal size at 10 weeks. They lack mature GHRH, have low pituitary growth hormone (GH) and hepatic insulin-like growth factor-1 mRNA levels and resemble phenotypically the "little" mouse (Gaylinn, B. D., Dealmeida, V. I., Lyons, C. E., Jr., Wu, K. C., Mayo, K. E. & Thorner, M. O. (1999) Endocrinology 140, 5066-5074) that has a mutant GHRH receptor. Despite a severe defect in pituitary proopiomelanocortin processing to mature adrenocorticotropic hormone, blood corticosterone levels are essentially normal. There is marked hyperproinsulinemia but without impairment of glucose tolerance. In contrast, PC2-null mice lack mature glucagon and are chronically hypoglycemic (Furuta, M., Yano, H., Zhou, A., Rouille, Y., Holst, J., Carroll, R., Ravazzola, M., Orci, L., Furuta, H. & Steiner, D. (1997) Proc. Natl. Acad. Sci. USA 94, 6646-6651). The PC1/3-null mice differ from a human subject reported with compound heterozygosity for defects in this gene, who was of normal stature but markedly obese from early life. The PC1/3-null mice are not obese. The basis for these phenotypic differences is an interesting topic for further study. These findings prove the importance of PC1/3 as a key neuroendocrine convertase.
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PMID:Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects. 1214 26


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