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)

Retinoblastoma protein (RB) is a tumor suppressor gene product involved in embryogenesis and cell cycle progression. One of the major mechanisms leading to RB dysfunction is complex formation with viral oncoproteins using the common RB binding motif Leu X Cys X Glu (LXCXE) which has also been identified in cellular ligands, e.g., RBP-1 and RBP-2. p107, a cellular protein with RB sequence homology, has been shown to bind to the same viral oncoproteins associating with RB and is therefore thought to contribute to cell cycle regulation. It has recently been suggested that insulin stimulates gene transcription through direct association with an, as yet, unidentified intracellular transcription factor. Due to the central roles of RB and p107 in coupling external growth signals with the progression of the cell cycle clock, we have hypothesized that these two proteins might be candidates for mediating the effects of insulin on DNA. We report here the identification of a region in the B-chain of human insulin that has the sequence LXCXE. Based on this finding we predict that the insulin B-chain may interact with RB and/or p107. Since we have also identified sequences hydropathically related to LXCXE in insulin-like growth factor I (IGF-I) and II (IGF-II), but not in relaxin, nerve growth factor, epidermal growth factor, glucagon or beta-endorphin, we further propose that both IGF-I and -II may assemble with RB and/or p107, too. Moreover, binding sites on RB and p107 identical with those suggested for viral oncoproteins and cellular ligands are predicted for insulin/IGF-I/IGF-II by using the hydropathic complementarity approach.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proposed interaction between insulin and retinoblastoma protein. 133 81

In order to identify insulin receptors in the bovine adrenal cortex and medulla, we have studied 125I-porcine insulin binding to the membrane preparations from the bovine adrenal cortex and medulla. 125I-porcine insulin bound not only to the bovine adrenal cortex but to the medulla in time-, temperature-, and pH-dependent manners. The maximum levels of 125I-porcine insulin binding in the two tissues were observed at 4 degrees C for 24 h of incubation, and its optimum pH ranged from 7.6 to 8.0. Under these conditions, at tracer concentration of porcine insulin (200 pg/ml), 10.4% and 6.6% of 125I-porcine insulin added to each reaction tube bound specifically to 10(5) x g-pellet fractions (microsomal membrane) from the cortical tissue (0.3 mg of protein) and from the medullary tissue (2 mg of protein), respectively. 125I-porcine insulin binding was observed predominantly in the microsomal membrane from the bovine adrenal cortex, and in a 15,000 x g- pellet fraction (synaptosomal membrane) from the bovine adrenal medulla. Scatchard analysis of binding data yielded curvilinear plots in each tissue. Analysis of curvilinear plots based on two sites model revealed similar affinity constant between the cortex and medulla. Receptor concentration of the cortex was several times higher than that of the medulla. In the two bovine adrenal tissues, human proinsulin and insulin-like growth factor I (IGF-I) had about 1/100 potency compared to porcine insulin in displacing 125I-porcine insulin binding. Porcine glucagon added with concentration up to 10(-6) M did not inhibit 125I-porcine insulin binding to both the cortex and the medulla.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of insulin receptors in the bovine adrenal cortex and medulla. 139 53

We report on a Japanese girl with short stature, malar hypoplasia, up-slanting palpebral fissures, blue sclerae and thin, stiff and slightly brownish hair. Short stature started in utero and her psychomotor development was normal. Menarche appeared at 13 years 8 months. Height at 14 years 5 months was 132 cm (-4.6 SD). Her growth hormone (GH) sleep pattern and responses to insulin, L-dopa, arginine, propranolol-glucagon and growth hormone-releasing hormone were normal. Plasma insulin-like growth factor I (IGF-I) was high (2170-4860 units/l) and increased from 4860 to 7080 units/l 20 h after biosynthetic GH injection. Gel infiltration patterns of the free and protein-bound IGF-I in plasma from the patient were not different from the controls; IGF-I fraction of the high and low molecular weight binding protein and the non-protein bound fraction were 75.5%, 15.8% and 8.7%, respectively. IGF-I from the patient showed normal bioactivities when determined by [35S]sulphate and [3H]thymidine uptake into cultured rat chondrocytes, and by [3H]thymidine and [3H]alpha-aminoisobutyric acid uptake into the patient's skin fibroblasts. IGF-I binding to cultured skin fibroblasts from the patient was comparable to that of controls. These results suggest that tissue specific defects of IGF-I receptors may be the cause of increased IGF-I levels in the patient.
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PMID:Short stature with normal growth hormone and elevated IGF-I. 139 82

Although insulin-like growth factor I increases renal function, the renal haemodynamic abnormality underlying the glomerular hyperfiltration in acromegaly is unknown. In normal subjects, amino acids and low doses of dopamine increase the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), presumably by a predominant vasodilation of the afferent and efferent glomerular arterioles, respectively. We studied baseline GFR and ERPF (determined with 125I-iothalamate and 131I-hippuran, respectively), the renal stimulatory effects of amino acid and dopamine infusion, and albuminuria before and after 3 months octreotide treatment in seven acromegalic patients with metabolically active disease. Octreotide reduced growth hormone concentrations from 14.7 +/- 3.0 to 5.5 +/- 1.0 micrograms l-1 (mean +/- SEM, n = 7; P less than 0.001) and insulin-like growth factor I levels from 4.12 +/- 1.31 to 2.44 +/- 0.68 kU l-1 (P less than 0.02). Glucagon concentrations did not change. Baseline GFR and ERPF declined from 132 +/- 5 to 117 +/- 6 and from 547 +/- 32 to 478 +/- 31 ml min-1 1.73 m-2, respectively (P less than 0.05 for both). Initially the response to amino acids was impaired (increment in GFR: 4.8 +/- 6.0%, NS; ERPF: -1.5 +/- 6.8%, NS), whereas the response to dopamine was normal (GFR: 10.6 +/- 1.1%, P less than 0.05: ERPF: 33.2 +/- 3.1%, P less than 0.01). After octreotide, amino acid infusion increased GFR by 15.0 +/- 6.8% (P less than 0.02) and ERPF by 11.3 +/- 5.6% (P less than 0.02), while the dopamine response was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a somatostatin analogue, octreotide, on renal haemodynamics and albuminuria in acromegalic patients. 151 98

The metabolic effects of recombinant human insulin-like growth factor I (rhIGF-I) on glucose, amino acid, and free fatty acid (FFA) metabolism were examined in nine healthy nonobese subjects. Each received a 3-h primed continuous infusion of rhIGF-I (20 micrograms/kg bolus, 0.4 microgram.kg-1.min-1) while maintaining euglycemia using an exogenous glucose infusion. Total IGF-I levels increased from 125 +/- 11 to 444 +/- 22 ng/ml, and free IGF-I levels rose from undetectable to 73 +/- 5 ng/ml. Insulin levels fell from 95 +/- 9 to 64 +/- 8 pM, and C-peptide fell from 453 +/- 48 to 206 +/- 29 pM; circulating glucagon levels also declined from 72 +/- 9 to 42 +/- 4 pg/ml, rhIGF-I produced a two- to threefold increase in glucose uptake as measured by [3H] glucose (from 10.3 +/- 0.6 to 27.4 +/- 3 mumol.kg-1.m-1), and, despite the fall in insulin secretion, there was a marked 60-70% inhibition of hepatic glucose production. Furthermore, FFA and branched-chain amino acids declined by 40-60% (411 +/- 58 to 165 +/- 36 and 406 +/- 23 to 219 +/- 14 microM, respectively). Our data demonstrate that rhIGF-I has potent effects on glucose (hepatic and peripheral), lipid, and amino acid metabolism in normal humans. The scope of the actions of rhIGF-I closely resemble those of insulin, despite a concomitant inhibitory effect on insulin secretion.
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PMID:Diverse effects of insulin-like growth factor I on glucose, lipid, and amino acid metabolism. 173 44

Achieving nitrogen accretion in patients with critical surgical illness or cancer cachexia is often not possible by the simple provision of calories and nitrogen. Cachexia may result from the metabolic derangements caused by release of inflammatory mediators such as tumor necrosis factor (TNF). We wished to determine whether recombinant human insulin-like growth factor I (rhIGF-I) preserves its protein-sparing effects in the face of high plasma TNF concentrations. Primed constant infusions of [15N]urea and [6-3H]glucose tracers were used to measure protein and glucose kinetics in fasted lambs. The lambs were divided into four groups: two groups received normal saline infusions of 480 min, and two groups received recombinant TNF (rTNF) infusions of 1 microgram.kg-1.h-1. During the last 300 min, one of the normal saline and one of the rTNF-infused groups were infused with rhIGF-I at a dose of 50 micrograms.kg-1.h-1. rTNF infusion resulted in the lambs becoming febrile and significantly increased plasma cortisol, glucagon, and insulin levels. rhIGF-I infusion in the control animals reduced the rate of loss of protein by 15% (P less than 0.01) and increased the rate of peripheral glucose clearance by 55% (P less than 0.01). rhIGF-I infusion in the rTNF-treated animals reduced the rate of net protein loss by 15% (P less than 0.01) and caused similar changes in glucose kinetics, as were observed in the control animals. We conclude that as rhIGF-I preserves its protein anabolic action in the face of high rTNF levels, further investigation into a possible clinical role for rhIGF-I in severe surgical illness is warranted.
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PMID:Effects of recombinant IGF-I on protein and glucose metabolism in rTNF-infused lambs. 195 85

We studied the effect of insulin, glucagon or dexamethasone on the production of insulin-like growth factor I (IGF-I) by cultured rat hepatocytes. Hepatocytes were isolated from normal adult rat livers and cultured in MEM, as nearly confluent monolayers. In the absence of such hormones, IGF-I and albumin accumulated in the culture medium almost linearly for periods up to 24 hours with the accumulation rates of 140 mU/mg cell protein per hour and 1.2 micrograms/mg cell protein per hour, respectively. Cycloheximide (5 micrograms/ml) almost completely inhibited the accumulation of IGF-I and albumin in the medium. Insulin at concentrations over 10(-10) M significantly inhibited the production of IGF-I in spite of the increased production of albumin. Conversely, glucagon stimulated the production of IGF-I at concentrations over 10(-8) M, but inhibited the production of albumin at concentrations over 10(-10) M. Dexamethasone stimulated the production of IGF-I at concentrations over 10(-7) M, but had no significant effects on the production of albumin. Thus, IGF-I production of hepatocytes is regulated by several hormones with different manner from albumin production.
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PMID:Effect of insulin, glucagon or dexamethasone on the production of insulin-like growth factor I in cultured rat hepatocytes. 206 Aug 98

The infusion of recombinant insulin-like growth factor I (IGF-I) causes a decrease in plasma glucose and insulin. In this study we examined whether or not IGF-I directly affects islet hormone release by means of a rat pancreas perfusion system. A superphysiologic concentration of IGF-I (2 nM) elicited a slight but significant decrease in insulin release under the perfusate glucose concentration of 120 mg/dl. A pharmacological concentration of IGF-I (200 nM) significantly suppressed the increase in insulin release in response to an increase in the perfusate glucose concentration (from 4.5 mM to 12.8 mM), but did not affect the decrease in insulin release in response to a decrease in the perfusate glucose concentration (from 6.9 mM to 2.8 mM). Glucagon release was not influenced by IGF-I in these experiments. These results suggest that IGF-I potentially inhibits the insulin release from islet B-cells directly, but its pathophysiological significance may be slight considering its partial inhibition at superphysiologic concentrations and its stable plasma level.
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PMID:Effects of insulin-like growth factor-I on insulin and glucagon release from isolated perfused rat pancreas. 210 92

1. Plasma levels of atrial natriuretic peptide and several other hormones were measured and related to the renal responses to chronic changes in the dietary intake of protein and sodium, alone and in combination. Eight healthy subjects consumed four diets for 1 week: a basal diet containing 140 mmol of sodium/day and 1 g of protein day-1 kg-1, the same diet with isocaloric addition of 1 g of meat protein day-1 kg-1, the basal diet with addition of 170 mmol of sodium chloride/day and the basal diet with both additions. 2. Creatinine clearance was increased significantly both by protein and, to a smaller extent, by sodium. Plasma atrial natriuretic peptide and the urinary excretion of guanosine 3':5'-cyclic monophosphate were increased significantly by sodium but were not affected by protein. Protein induced a significant rise in plasma glucagon levels, whereas the rise in somatomedin C (insulin-like growth factor I) just failed to reach statistical significance. 3. These findings demonstrate that atrial natriuretic peptide does not mediate chronic protein-induced hyperfiltration, although it may contribute to the renal effects of sodium. Glucagon and somatomedin C (insulin-like growth factor I) may have contributed to chronic protein-induced hyperfiltration.
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PMID:Atrial natriuretic peptide and chronic renal effects of changes in dietary protein and sodium intake in man. 216 88

GRF promotes follicular maturation and ovulation when administered with FSH in the treatment of infertility. Such actions could be mediated by stimulation of GH secretion and insulin-like growth factor I production, but the known actions of the structurally related hormone, vasoactive intestinal peptide (VIP), on granulosa cell function suggested that GRF may also act directly on the ovary to stimulate follicular development. Radioligand binding and activation studies, performed in granulosa cells from immature estrogen-treated rats, revealed a common receptor for VIP and rat (r) GRF in the ovary. Specific binding of [125I]VIP to granulosa cells was saturable and dependent on time and temperature. The relative potencies of VIP-related peptides for inhibition of radioligand binding were: VIP greater than rGRF greater than peptide histidine isoleucinamide greater than [His1,Nle27] human GRF(1-32)NH2 greater than secretin. In binding studies with the potent GRF agonist, [125I] [His1,Nle27]GRF(1-32)NH2, relative potencies were: rGRF(1-43)OH greater than [His1,Nle27]human GRF(1-32)NH2 greater than VIP greater than peptide histidine isoleucinamide greater than secretin. Glucagon and gastric inhibitory peptide, other peptides of the glucagon superfamily, and unrelated peptides including CRF and beta-endorphin, did not inhibit binding of either radioligand to ovarian receptors. In cultured granulosa cells, rGRF and VIP stimulated cAMP formation, consistent with coupling of their receptors to the adenylate cyclase system, and potentiated FSH-induced cAMP production. Both peptides also amplified FSH-induced progesterone biosynthesis, aromatase activity, and LH receptor formation. These observations demonstrate that rGRF is a potent cAMP-mediated agonist in the rat ovary and acts on a common VIP/GRF receptor in maturing granulosa cells. It is likely that the potentiating effect of administered GRF on gonadotropin-stimulated follicular development in vivo is in part mediated by direct actions of the peptide on the VIP/GRF receptor. Also, since GRF is present in the gonads, it is possible that the locally-produced peptide promotes follicular maturation by paracrine modulation of the stimulatory action of FSH on granulosa cell function.
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PMID:Receptor-mediated actions of growth hormone releasing factor on granulosa cell differentiation. 217 7


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