Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Young Wistar rats were used as an experimental model to determine the effects of protein-energy malnutrition on glucose tolerance and insulin release. 2. Malnourished rats presented some of the features commonly found in human protein-energy malnutrition, such as failure to gain weight, hypoalbuminaemia, fatty infiltration of the liver and intolerance of oral and intravenous glucose loads. 3. The rate of disappearance of glucose from the gut lumen was greater in the malnourished rats but there was no significant difference in portal blood glucose concentration between normal and malnourished rats 5 and 10 min after an oral glucose load. 4. Insulin resistance was not thought to be the cause of the glucose intolerance in the malnourished animals since these rats had a low fasting plasma insulin concentration with a normal fasting blood glucose concentration and no impairment in their hypoglycaemic response to exogenous insulin administration. Furthermore, fasting malnourished rats were unable to correct the insulin-induced hypoglycaemia despite high concentrations of hepatic glycogen. 5. Malnourished rats had lower peak plasma insulin concentrations than normal control animals after provocation with oral and intravenous glucose, intravenous tolbutamide and intravenous glucose plus aminophyllin. This was not due to a reduction in the insulin content of the pancreas or potassium deficiency. Healthy weanling rats, like the older malnourished rats, had a diminished insulin response to intravenous glucose and intravenous tolbutamide. However, their insulin response to stimulation with intravenous glucose plus aminophyllin far exceeded that of the malnourished rats. Thus the impairment of insulin release demonstrated in the malnourished rats cannot be ascribed to a 'functional immaturity' of the pancreas.
Clin Sci Mol Med 1976 Mar
PMID:Glucose tolerance and insulin release in malnourished rats. 81 69

1. Intravenous glucose tolerance test were performed in fourteen patients with mild or moderate liver damage due to paracetamol overdose. 2. In patients managed conservatively there was glucose intolerance associated with a diminished early insulin response to glucose, suggesting inadequate nutrition in the period between the overdose and the glucose tolerance test. 3. Patients given intravenous glucose supplements to maintain nutrition were also glucose intolerant and, in these, insulin responses to glucose were normal. The decreased fractional disappearance rate was partly due to an increase in glucose distribution space and partly due to a decrease in absolute glucose disappearance rate. 4. Impaired gluconeogenesis was suggested by mild fasting hypoglycaemia in four patients and raised fasting blood lactate concentrations. Serum growth hormone concentrations showed a paradoxical increase after glucose. 5. All these variables had returned to normal in four patients re-tested after recovery.
Clin Sci Mol Med 1975 Nov
PMID:Disturbances in glucose metabolism in patients with liver damage due to paracetamol overdose. 119 5

A modified human growth hormone (hGH) that lacks the first 43 residues of the intact hormone was prepared by recombinant-DNA technology. For preparative purposes an additional alanine was made the amino terminal residue. Sequence analysis and tryptic peptide mapping combined with amino acid analyses confirmed the structure of the polypeptide. Less than 2% N-terminal methionine was detected. The hGH44-191 was estimated to be at least 10 times more active than hGH in producing glucose intolerance in obese yellow mice (Avy/A) and was equipotent to hGH in increasing serum free fatty acids in fasted, hypophysectomized rats. The peptide did not promote growth in hypophysectomized rats nor did it exhibit early (1h) insulin-like activity in fasted, hypophysectomized rats, as indicated by its failure to lower blood glucose and fatty acids. The modified hGH was inactive in the Nb-2 cell assay but was about one-third as active as hGH in stimulating the pigeon crop sac. In radioimmunoassays using 125I-labeled hGH and polyclonal antibodies to intact hGH, cross-reactivity of hGH44-191 was less than 1%. We conclude that removal of the amino terminal portion of hGH enhances its diabetogenic properties, and that this activity does not depend upon the ability to promote growth. Furthermore, the insulin-like activity can be separated from its diabetogenic action by deletion of the first 43 amino terminal residues. This is the first report of a modified hGH that has anti-insulin effects greater than hGH itself.
Mol Cell Endocrinol 1991 Jun
PMID:A recombinant-DNA-derived modification of human growth hormone (hGH44-191) with enhanced diabetogenic activity. 193 24

Glucose tolerance was studied in transgenic mice (SJL x C57BL/6) expressing human GH under the control of a housekeeping promoter. Parental SJL mice were found to harbour a dominant allele, termed here glid, determining glucose intolerance in pure-bred animals and in F1 hybrids with glucose-tolerant C57BL/6 mice. Blood glucose levels in transgenic SJL x C57BL/6 hybrid mice were well controlled following glucose challenge, whereas non-transgenic hybrids failed to control their glucose adequately. Pancreatic morphology was normal in all animals. In confirmation of a physiological role for GH in glucose regulation. GH-deficient lit/lit mice were pathologically sensitive to glucose.
J Mol Endocrinol 1991 Apr
PMID:Abrogation of dominant glucose intolerance in SJL mice by a growth hormone transgene. 204 41

There is a general slowing of protein biosynthesis with increasing age that appears to be universal and involved in the mechanism of aging. One of the apparent expressions of this aging mechanism is an age-related decreased induction of many enzymes including, as the focus of this analysis, those of carbohydrate metabolism. The impaired induction of these enzymes contributes to the slowing of several carbohydrate metabolic pathways, and parallels a marked age-related diminution in the generation of anabolic metabolites and energy compounds from these pathways. Intracellular carbohydrate metabolism contributes to the synthesis of virtually all macromolecules of the cell, and the age-related slowing and impairment in carbohydrate metabolism appears to play a role in the expression of cellular senescence. Moreover, these intracellular impairments in the aged contribute, in part, to the expression of several physiologic decrements and pathologies that accompany the aging process, such as glucose intolerance and diabetes.
Mol Biol Med 1987 Oct
PMID:Gene expression of carbohydrate metabolism in cellular senescence and aging. 332 Jun 74

Studies were conducted to assess the renal functional state in two recently discovered diabetic chimpanzees. Both were nonobese, adult female animals with the non-insulin-dependent form of impaired glucose tolerance, analogous to the Type II or nonobese, maturity-onset diabetes of humans. Both animals displayed moderate-to-heavy proteinuria and glycosuria in response to intravenous administration of glucose or tolbutamide. Chimpanzee number 333, but not number 1037, had fasting proteinuria and chronic hypertension. Renal function studies, using the inulin clearance method, demonstrated significantly decreased glomerular filtration rates and elevated rates of sodium excretion for both animals. The rate of chloride excretion was also elevated in animal number 1037, but potassium excretion was apparently unaffected in both animals. Abnormal serum biochemical parameters demonstrated for chimpanzee number 333 included elevations in calcium, magnesium, creatinine, urea nitrogen, and uric acid; animal number 1037 had only an elevated serum creatinine. Results are consistent with the occurrence of renal disease similar to the nephropathy that develops in human diabetics. The difference in severity of renal impairment in the two chimpanzees is possibly related to differences in duration and severity of impaired glucose tolerance. A progression of both diabetic and renal disorders is most probable.
Exp Mol Pathol 1983 Apr
PMID:Impaired renal function in diabetic chimpanzees (Pan troglodytes). 683 45

Age is known to be associated with the development of glucose intolerance. In this review an effort has been made to differentiate between the effects of age per se on glucose tolerance, as distinguished from those of such age-related variables as obesity, diet, development of frank diabetes, etc. At the same time, an attempt was made to evaluate the evidence implicating abnormalities of insulin secretion and/or insulin action in the development of glucose intolerance with age. It is concluded that the questions being asked are far from simple, and that available data do not provide unequivocal answers.
Mol Cell Biochem 1980 May 28
PMID:Effects of age on various aspects of glucose and insulin metabolism. 699 16

The effects of an overexpressed, non-insulin-responsive gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (GTP) (PEPCK; EC 4.1.1.32), on glucose homeostasis were investigated. Transgenic rats harboring a metallothionein-driven PEPCK gene (lacking the entire PEPCK upstream-regulatory region) expressed transgene PEPCK mRNA in the key gluconeogenic tissues, liver and kidney. Female transgenic rats, studied at 10 weeks of age, showed mild fasting hyperglycemia (6.9 +/- 0.2 vs. 5.9 +/- 0.1 mM P = 0.002 n = 6), hyperinsulinemia (92.2 +/- 4.0 vs. 54.0 +/- 6.6 pM, P = 0.001, n = 6), impaired glucose tolerance and increased weight gain (178.3 +/- 3.2 vs. 153.4 +/- 2.5 g, P = 0.001, n = 16 and n = 13 transgenic and control rats, respectively). Despite hyperinsulinemia at this age, kidneys of transgenic rats maintained a significant 20% elevation of total PEPCK enzyme activity, while total liver PEPCK activity was not reduced. This study suggests that an insulin-resistant step in the gluconeogenic pathway can lead to glucose intolerance and an increase in weight. These rats offer the unique opportunity to study the metabolic consequences of chronic, mild excess glucose supply, as seen in non-insulin-dependent diabetes.
Mol Endocrinol 1995 Oct
PMID:Impaired glucose tolerance and increased weight gain in transgenic rats overexpressing a non-insulin-responsive phosphoenolpyruvate carboxykinase gene. 854 47

In order to elucidate the implication of GLUT2 in the impaired glucose metabolism caused by ethanol, we examined if ethanol affects GLUT2 glucose transporter mRNA expression in the liver. After the adult rats were fed with and/or without ethanol for 1 or 4 weeks, hepatocytes were isolated and total RNA was extracted from them. The levels of GLUT2 mRNA in hepatocytes isolated from 1 week-ethanol fed rats estimated by Northern blot analysis did not change compared to those of untreated rats, those levels in hepatocytes from 4 weeks-ethanol fed rats decreased markedly. Studies were also performed using primary rat hepatocyte cultures in vitro. We found that ethanol, when added to cultured hepatocytes, resulted in a substantial reduction in the levels of GLUT2 mRNA and this effect was only observed after 24 hr exposure of ethanol. Thus, ethanol seems to have a direct inhibitory effect on GLUT2mRNA in the liver, which may eventually cause the impaired glucose tolerance.
Biochem Mol Biol Int 1995 Nov
PMID:Ethanol decreases the levels of GLUT2 glucose transporter mRNA in hepatocytes. 858 40

The effects of glucose on Ca2+ATPase activity of erythrocyte membranes were investigated under in vitro and in vivo conditions. Results of the study, in vitro, showed that Ca2+ATPase activity of erythrocyte membrane was decreased by increasing glucose concentrations (0-30 mM). When glucose-6-phosphate (0-100 mM) was used instead of glucose no significant change occurred in Ca2+ATPase activity. Tunicamycin (0.01 ng/ml) when added to the incubation media together with glucose prevented the decrease in Ca2+ATPase activity. The results of the studies in vivo showed that Ca2+ATPase activities of both male and female subjects with normal or impaired glucose tolerance were changed with time in a complex manner after an oral glucose loading. However, Ca2+ATPase activities of the subjects with impaired glucose tolerance were smaller than those of the corresponding normal controls even before glucose administration.
Biochem Mol Biol Int 1996 Jun
PMID:Effects of glucose on the activity of erythrocyte membrane Ca2+ATPase in subjects with normal and impaired glucose tolerance. 882 6


1 2 3 4 5 6 7 8 9 10 Next >>