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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of starvation and refeeding and of obesity on pancreatic alpha2- and beta-cell responses to glucose or tolbutamide were studied with the isolated rat or mouse pancreas perfused with an amino acid mixture in the presence and absence of glucose. It was observed that the physiological adaptation to a regimen of fasting and realimentation and to obesity differed greatly in the two types of endocrine cells. Whereas beta-cells of rats showed a dramatic reduction of glucose- and tolbutamide-stimulated insulin release during starvation that was reversed by refeeding, alpha2-cells preserved their response to stimulators and inhibitors during this experimental manipulation. Amino acid stimulation of glucagon release occurred equally well with the pancreas from fed and starved rats and was suppressed efficiently by glucose and tolbutamide in both nutritional states. Surprisingly, the rate of onset of glucose suppression of alpha2-cells was significantly higher in the fasted than in the fed state. This glucose hypersensitivity was apparent 2 d after after food deprivation and had disappeared again on the 2nd d of refeeding. In the pancreas from animals starved for 3 d, glucose and tolbutamide suppression of alpha2-cells took place in the absence of demonstrable changes of insulin release. In the isolated perfused pancreas taken from the hyperphagic obese hyperglycemic mouse (C57 Black/6J; ob/ob), the observed rate of insulin secretion as a result of a combined stimulus of amino acids and glucose and of glucagon release stimulated by amino acids was about four times higher than achieved by the pancreas of lean controls. However, glucose was unable to suppress the alpha2-cells in the pancreas of obese animals, in spite of the hypersection of the beta-cells, again in contrast to the alpha2-cells of controls that were readily inhibited by glucose. These data imply that the acute suppression of alpha2-cells by glucose is largely independent of a concomitant surge of extracellular insulin levels and that the adaptation of the islet organ to starvation leads to decreased glucose sensitivity of beta-cells, which contrasts with an improved glucose responsiveness of alpha2-cells. However, hyperphagia, which is assumed to be the primary abnormality in the ob/ob mouse, leads to overproduction of insulin and glucagon by the pancreas while greatly reducing the alpha2-cell sensitivity to glucose. An attempt is made to incorporate these data on starvation, refeeding, and obesity, as well as previous results with experimental diabetes, in a comprehensive picture describing a regulative principle underlying the glucose responsivness of alpha2-cells.
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PMID:Adaptations of alpha2- and beta-cells of rat and mouse pancreatic islets to starvation, to refeeding after starvation, and to obesity. 698 16

The existence of a relationship between the ventromedial hypothalamic area (VMH) and the activity of the endocrine pancreas has been shown previously. This relationship has been further tested and extended in the present study, using isolated perfused pancreases from rats previously lesioned (4-7 d) in the VMH. It was found that in isolated pancreases obtained from rats fed ad lib. for 4 d after VMH lesions (i.e., that were hyperphagic), the typical biphasic pattern of insulin secretion was observed following glucose stimulation (20 mM) and that the total insulin output was much greater than that of controls. The increased insulin output was not a result of hyperphagia because similar results were obtained using pancreases obtained from VMH-lesioned rats in which a food restriction matching exactly that of control rats was started either immediately of 3 d after the lesions. Pancreases from such food-restricted VMH-lesioned rats oversecreted insulin, when compared with controls fed the same amount, from 7 mM of glucose concentration in perfusion medium onwards. After the addition of arginine (10 mM), the total output of glucagon by pancreases from food-restricted VMH-lesioned rats was twice that of controls. Qualitatively, the arginine-induced glucagon secretion by pancreases from food-restricted VMH-lesioned rats retained its biphasic pattern. Similarly, epinephrine (0.1 muM) elicited a greater glucagon release by pancreases from food-restricted VMH-lesioned rats when compared with controls. These data further support the concept of a link (as yet undefined) between the hypothalamus and the endocrine pancreas, as lesions of the VMH area resulted in abnormal secretion not only of insulin, but of glucagon as well.
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PMID:Consequences of ventromedial hypothalamic lesions upon insulin and glucagon secretion by subsequently isolated perfused pancreases in the rat. 698 69

A spontaneous recessive mutation appearing in strain 129/J mice at the diabetes (db) locus on Chromosome 4 has been characterized. The new allele, designated db3J, produced hyperphagia and severe obesity. Mutants weighed in excess of 70 g by 6 months of age, compared to 22-28 g for lean littermates. Although the disease was similar to the mild hyperglycaemia-severe obesity syndrome exhibited by db gene presentation on the C57BL/6J inbred background, the syndrome in 129/J mice reduced lifespan, with mutants exhibiting sudden weight loss, hypoglycaemia, and a 67% mortality between 6 and 14 months of age. Mutant males, but not females, were transiently hyperglycaemic between 2 to 4 months of age, attaining a maximum mean blood sugar of 196 +/- 27 (SEM) mg/dl. Thereafter glucose levels declined to normoglycaemic values (80-100 mg/dl), and with increasing age, mutants of both sexes became hypoglycaemic (60 mg/dl at 9 months). Mutants of both sexes were extremely hyperinsulinaemic at the earlier ages, with mean plasma insulin at months 5 reflecting 30-fold elevations above normal for males and 18-fold for females. These levels diminished with age, the decline being more marked in males. Plasma glucagon levels were 3-fold elevated in the younger mutants of both sexes (86 pg/ml versus 28 pg/ml in normal mice), mean levels increasing to almost 5-fold above mean control vaues in the older age group (198 pg/ml versus 41 pg/ml in normal mice). Histopathological findings were limited to pancreas. Increasing necrosis of the exocrine, but not endocrine, pancreas was noted in aging mutants. Aldehyde fushsin staining of the mutant pancreas revealed hyperplastic islets filled with heavily granulated B-cells. B-cell hyperplasia was accompanied by a 30-fold increase over controls in pancreatic insulin content in the 8 month old mutants, whereas pancreatic glucagon content was only doubled. Morphometric analysis showed less than a 2-fold increase in the mean number of A-cells per islet. Thus, an interesting feature of expression of the diabetes gene in the 129/J strain is the persisting hyperglucagonaemia in the face of moderating hyperinsulinaemia.
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PMID:A new mutation (db3J) at the diabetes locus in strain 129/J mice. I. Physiological and histological characterization. 699 69

Expression of the obese hyperglycaemic (bo/ob) syndrome in mice is modified by the background genome. The Aston colony carries the ob gene on a mixed background which produces a unique combination of different features shown by ob/ob mice on other backgrounds. The maximum body weight of Aston ob/ob mice exceeded that of other colonies, possibly reflecting a trait for higher growth rate in the background genome. The hyperphagia, marked hyperinsulinaemia and moderate hyperglycaemia observed during the development of the syndrome receded in old mice. Plasma glucagon concentrations in the fed state were similar to +/+ mice and did nor Vary throughout life. Hyperplasia of the B-cells increased inordinately during the development of the syndrome, but declined in older mice coincident with progressive intercellular vacuolation and the appearance of acinar-like cells within the islets. A-cell hyperplasia was greater in young mice, and A-cells became relocated throughout the islets of older mice. The distinct pattern of age-related changes in ob/ob mice indicates that experiments using this gene type should define clearly their age as well as genetic background.
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PMID:Influence of genetic background and age on the expression of the obese hyperglycaemic syndrome in Aston ob/ob mice. 704 Feb 65

The effects of long-term exposure (7 wk) to hyperinsulinaemia on insulin sensitivity were studied in female rats. The rats were made hyperinsulinaemic by implantation of osmotic minipumps that were changed once a week. Elevated adrenergic activity and secretion of glucocorticoids were controlled by another minipump with propranolol and adrenalectomy with corticosterone substitution, respectively. This resulted in hyperinsulinaemia and moderate hypoglycaemia, the latter probably counteracted by overeating and increased glucagon secretion, as indicated by increased body weight and lower liver glycogen contents, respectively. Euglycaemic, hyperinsulinaemic clamp measurements showed a significantly higher glucose disposal rate (P < 0.05) in the hyperinsulinaemic rats 18.8 +/- 1.1 mg kg-1 min-1 compared with the control groups 14.6 +/- 0.4 and 15.4 +/- 0.9 mg kg-1 min-1. Insulin stimulation of 2-deoxyglucose as well as glycogen synthesis was measured in the extensor digitorum longus muscle, the red and white part of the gastrocnemius, the soleus muscle, the liver and in parametrial, retroperitoneal, and inguinal adipose tissue. No differences were found between the groups in the insulin response of the 2-deoxyglucose uptake. Glycogen synthesis was significantly elevated in all muscles in the insulin treated compared with the control rats but no differences were found in the liver. Capillary density was significantly elevated per unit muscle surface area in the soleus and extensor digitorum longus muscles of the insulin-exposed rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of long-term hyperinsulinaemia on insulin sensitivity in rats. 762 70

The diabetogenic effects of streptozotocin (STZ) were studied on blood glucose, plasma insulin, feeding and drinking, body weight, islet morphology, and hypothalamic serotonin (5-HT) release in vehicle-pretreated rats and in rats pretreated with either intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT; a 5-HT nerve fiber depletor), intraperitoneal injection of p-chlorophenylalanine (PCPA; a tryptophan hydroxylase inhibitor), or intraperitoneal injection of p-chloroamphetamine (PCA; a neurotoxin for 5-HT nerve fiber). At four days after STZ administration, vehicle-treated rats displayed hyperglycemia, polydipsia, polyphagia, decreased plasma insulin level, derangement of islet morphology (few insulin cells, accumulation of glucagon cells), and elevated 5-HT release in the hypothalamus. The above diabetogenic effects of STZ were attenuated by brain serotonin depletion induced by 5,7-DHT, PCPA, or PCA. Furthermore, the STZ-induced hyperglycemia or derangement of islet morphology was attenuated by peripheral sympathectomy or adrenalectomy. It is concluded that brain serotonin depletion attenuates diabetogenic effects of STZ by reducing sympathetic efferent activity in rats.
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PMID:Brain serotonin depletion attenuates diabetogenic effects of streptozotocin. 776 35

Clinical studies and experiments in rats were carried out to elucidate changes in fuel utilization after hepatectomy. In addition, the effect of glucose hyperalimentation on energy metabolism in the liver remnant was studied. Respiratory quotient (RQ) and substrate oxidation rate for fat and glucose were evaluated by indirect calorimetry in eight patients who had undergone liver resection. Patients had a reduced nonprotein RQ of approximately 0.85 and a reduced ratio of glucose to fat oxidation of approximately 2.0 on the 1st and 2nd postoperative days. After 80% hepatectomy, rats received either 30 kcal.kg-1.day-1 (group 1) or 200 kcal.kg-1.day-1 (group 2) of glucose for 48 h. In both rat groups, hepatic mitochondrial ATP synthesis 12 and 24 h after hepatectomy was accelerated when palmitic acid was used as the substrate and suppressed when pyruvate was used compared with sham-operated groups. This suggests that the energy substrate of the remnant liver was principally fatty acids rather than glucose, which seems to occur also in humans. Hepatic energy charge was within normal limits in group 1 (0.862 +/- 0.008) but decreased significantly in group 2 (0.818 +/- 0.006, p < 0.01) 12 h after hepatectomy. An abundance of glucose in the early postoperative period therefore caused a hepatic energy derangement by suppressing endogenous fat oxidation. This suppression was corroborated by the findings of lower immunoreactive glucagon and nonesterified fatty acid concentration in group 2. Therefore, glucose hyperalimentation in the early postoperative period after liver resection is not recommended.
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PMID:Fuel utilization and glucose hyperalimentation after liver resection. 781 53

The purpose of the present investigation was to study the role of two potential contributory factors, hyperphagia and alterations in fuel metabolism, on the development of tissue trace element accumulation in the experimentally induced diabetic rat. The role of increased mineral intake associated with diabetic hyperphagia on tissue trace element accumulation was evaluated by feeding control and diabetic rats high-carbohydrate (HC) diets which varied in Zn, Cu, Mn, and Mg concentrations. Diabetic rats were hyperphagic and had lower plasma Mg, and higher liver Zn, Cu, and Mn concentrations than control rats, regardless of dietary mineral intake. In a second study, diabetic hyperphagia was reduced by feeding control and diabetic rats a HC, high-fat (HF), or high-protein (HP) diet; the effects of altering diabetic metabolism on trace element status was studied. Liver Mn and Zn concentrations of diabetic rats fed the HF diet were lower than diabetic rats fed the HC diet and HP diet, and were similar to control rats. Liver Cu concentrations of diabetic rats fed the HF and HP diets were lower than diabetic rats fed the HC diet and were similar to control rats. While diabetic rats, in general, had higher plasma glucagon concentrations and lower percent body fat than control rats, diabetic rats fed the HF diet had similar plasma glucagon and percent body fat to control rats. These data suggest that tissue-specific biochemical needs, such as the need for metals as cofactors for enzymes, rather than hyperphagia per se, may drive the accumulation of trace elements in the diabetic animal.
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PMID:Dietary macronutrient composition influences tissue trace element accumulation in diabetic Sprague-Dawley rats. 793 39

Physiologic control of eating involves neural and chemical regulators that may have therapeutic applications in weight control. Information on the nature and quantity of ingested and stored nutrients is relayed to the brain via sensory nerve fibers. This information is integrated at specific centers in the brain, then impulses in motor nerve fibers are discharged leading to initiation or termination of eating. Chemical regulators of eating behavior include gastrointestinal peptides released during digestion, absorbed glucose circulating in the plasma, and the hormonal regulators of glucose metabolism (insulin and glucagon). There is, however, considerable interplay between neural and chemical processes in regulation of food intake. Neural mechanisms are evidently mediated by chemical regulators, because neurotransmitters, including serotonin, allow nerve impulses to cross synapses. In addition, some chemical regulators are concentrated at brain centers that are implicated in regulation of eating behavior. Although some gastrointestinal peptides and serotoninergic drugs have been used to treat obesity, the existence of a complex control system with alternate mediators of food intake suggests that a single therapeutic agent is unlikely to be applied universally to suppress overeating.
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PMID:Physiologic control of food intake by neural and chemical mechanisms. 809 42

Statistical studies repeatedly have shown an association between systemic insulin resistance and a preponderance of highly glycolytic, relatively insulin-insensitive muscle fibers as well as a low density of muscle capillaries. The nature of the relationship between these observations is, however, not clear. Female rats were made hyperinsulinemic for 7 days by implantation of osmotic minipumps. Elevated adrenergic activity and secretion of glucocorticoids were controlled by another minipump with propranolol and adrenalectomy was controlled with glucocorticoid substitution. This resulted in hyperinsulinemia and moderate hypoglycemia, the latter probably counteracted by overeating and increased glucagon secretion, as indicated by increased body weight and lower liver glycogen contents, respectively. Systemic insulin sensitivity was increased and measured with a hyperinsulinemic-euglycemic clamp technique. This was paralleled by an elevated glucose utilization estimated as uptake of 2-deoxyglucose in parametrial, retroperitoneal, and inguinal adipose tissues and the soleus and extensor digitorum longus muscles. Glycogen synthesis was also elevated in the soleus muscle. Muscle fiber composition changed with hyperinsulinemia and elevated 2-deoxyglucose uptake toward more fast-twitch, type II, particularly type IIb fibers, whereas the proportion of slow-twitch, type I fibers, diminished. Capillary density was elevated per unit muscle surface area as well as per muscle fiber. This was paralleled by increased insulin sensitivity systemically and in muscles. These results suggest that muscle fiber composition alterations may be a consequence rather than a cause of hyperinsulinemia and that capillarization rather than fiber composition is of importance for insulin sensitivity in muscle.
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PMID:Effects of hyperinsulinemia on muscle fiber composition and capitalization in rats. 851 74


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