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  • 1
    ISSN: 1432-0428
    Keywords: Hyperglycaemia ; islet cell function ; insulin ; glucagon ; diabetic remissions ; Type 1 diabetes ; Type 2 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is postulated that hyperglycaemia influences the natural history of Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus. Hyperglycaemia, even when mild, can attenuate the secretory response of pancreatic β and α cells to increments in glucose and can impair insulin-mediated glucose transport, thus impeding its own correction and initiating a cycle of progressive self-exacerbation and metabolic deterioration. Both reduced islet function and insulin action may be the consequence of a generalized down-regulation and/or occupation of glucose transporters by hyperglycaemia so that the islets respond less to further increments in glycaemia. The postulated hyperglycaemic cycle can be initiated by any environmental perturbation that increases insulin demand in previously normoglycaemic patients in whom insulin secretion has already reached a maximum level of compensation for peripheral insulin resistance (as in obese pre-Type 2 diabetes) or for a reduced β-cell mass (as in pre-Type 1 diabetes). Elimination of hyperglycaemia by any means can halt this cycle of progressive metabolic deterioration and may restore transiently metabolic recompensation both in Type 1 and Type 2 diabetes. There is experimental evidence that long-standing severe hyperglycaemia may irreversibly damage β cells.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Glucagon-like immunoreactivity (GLI) ; glucagon ; insulin ; triglyceride ; glucose ; fat ; protein meal ; somatostatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of somatostatin on GLI release during the absorption of intraduodenally administered glucose, casein hydrolysate and longchain triglycerides were studied in conscious dogs. Whereas, after an intraduodenal glucose load, GLI rose promptly in saline-infused control experiments to a peak of 5 ng/ml (SEM ± 4) in 60 minutes, significantly lower values were observed during somatostatin infusion (P〈0.025 – 0.05). A similar reduction in the magnitude of the GLI response to intraduodenally administered casein hydrolysate (P〈0.05) and fat (p〈0.05) was observed.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 20 (1981), S. 1-11 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 21 (1981), S. 1-11 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: GLUT 2 ; Zucker rats ; caloric restriction ; beta-cell depletion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pre-diabetic male Zucker diabetic fatty rats (ZDF) become diabetic between 8 and 10 weeks of age. At that time their beta cells exhibit high basal insulin secretion, absent insulin response to glucose and loss of GLUT 2 glucose transporter. Beta-cell volume, which is increased at the onset of non-insulin-dependent diabetes, declines precipitously by age 18 weeks. To determine if expression of this diabetic phenotype was dependent upon the increased food intake of these rats, they were diet-matched to lean littermates for 12 weeks beginning at 6 weeks of age. Untreated control ZDF rats received an unrestricted diet for 3 months. All of the controls became hyperglycaemic by 8 weeks of age, whereas all diet-matched rats remained euglycaemic throughout the 3 months, despite the fact that at 18 weeks of age their mean body weight equaled that of obese rats on an unrestricted diet. In the former rats glucose-stimulated insulin secretion was absent at 12 weeks of age and GLUT-2-positive beta cells had fallen below 30%. The volume fraction of their beta cells was 2.6 times normal at this age but by 18 weeks of age it had declined by 75%. Diet restriction for 3 months prevented the loss of glucose-stimulated insulin secretion and the reduction of beta-cell GLUT-2 and beta-cell volume fraction. However, neither the elevated basal insulin secretion nor the exaggerated arginine-stimulated insulin secretion of the obese rats was reversed or prevented by caloric restriction. We conclude that in diabetic ZDF rats the glucose incompetence of beta cells and the reduction of beta-cell GLUT 2, which coincide with the onset of hyperglycaemia, and the subsequent loss of beta-cell volume, occur only when the caloric intake is excessive. The increased basal insulin secretion and exaggerated insulin response to arginine appear to be relatively independent of caloric intake.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Key words GLUT 2 ; Zucker rats ; caloric restriction ; beta-cell depletion.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pre-diabetic male Zucker diabetic fatty rats (ZDF) become diabetic between 8 and 10 weeks of age. At that time their beta cells exhibit high basal insulin secretion, absent insulin response to glucose and loss of GLUT 2 glucose transporter. Beta-cell volume, which is increased at the onset of non-insulin-dependent diabetes, declines precipitously by age 18 weeks. To determine if expression of this diabetic phenotype was dependent upon the increased food intake of these rats, they were diet-matched to lean littermates for 12 weeks beginning at 6 weeks of age. Untreated control ZDF rats received an unrestricted diet for 3 months. All of the controls became hyperglycaemic by 8 weeks of age, whereas all diet-matched rats remained euglycaemic throughout the 3 months, despite the fact that at 18 weeks of age their mean body weight equaled that of obese rats on an unrestricted diet. In the former rats glucose-stimulated insulin secretion was absent at 12 weeks of age and GLUT-2-positive beta cells had fallen below 30 %. The volume fraction of their beta cells was 2.6 times normal at this age but by 18 weeks of age it had declined by 75 %. Diet restriction for 3 months prevented the loss of glucose-stimulated insulin secretion and the reduction of beta-cell GLUT-2 and beta-cell volume fraction. However, neither the elevated basal insulin secretion nor the exaggerated arginine-stimulated insulin secretion of the obese rats was reversed or prevented by caloric restriction. We conclude that in diabetic ZDF rats the glucose incompetence of beta cells and the reduction of beta-cell GLUT 2, which coincide with the onset of hyperglycaemia, and the subsequent loss of beta-cell volume, occur only when the caloric intake is excessive. The increased basal insulin secretion and exaggerated insulin response to arginine appear to be relatively independent of caloric intake. [Diabetologia (1995) 38: 173–179]
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Alpha cells ; glucagon ; anti-insulin serum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine the effect of neutralization of endogenous insulin upon the glucagon response to a rise and fall of glucose concentration, pancreata isolated from normal rats were perfused with either a potent anti-pork insulin guinea pig serum or a nonimmune guinea pig serum for 30 min. During this period glucose concentration was changed from 100 mg/dl to either 130, 180 or 80 mg/dl for 10 min. Antiserum perfusion at 100 mg/dl caused an approximately two-fold increase in glucagon which was not suppressed by an increase in glucose concentration to either 130 or 180 mg/dl, although glucagon secretion was significantly suppressed in the control experiments in which nonimmune serum was perfused. However, the 0.38±0.21 ng/min rise in glucagon secretion in response to a reduction in glucose concentration to 80 mg/dl in the control experiments was not abolished by antiserum perfusion but, instead, was enhanced (2.66±0.60 ng/min). These findings suggest that insulin may be required for glucose-mediated suppression of glucagon in the isolated pancreas of normal rats but not for stimulation of glucagon secretion by mild glucopenia. Alternatively, neutralization of insulin-mediated release-inhibition of glucagon secretion may simply have altered alpha cell responsiveness in a direction that desensitized it nonspecifically to suppression and sensitized it to stimulation.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Autonomic nervous system ; intrinsic ganglia ; small granulated cells ; catecholamines ; islets of Langerhans ; electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electron microscopic examination of the intrinsic autonomic ganglia of the rat pancreas revealed the presence of small cells, when compared to the principal ganglionic neurons, within a particular type of ganglia. The small cells were often located in clusters around fenestrated capillaries, but their most striking characteristic was the presence of catecholamine-like granules distributed throughout the cytoplasm. The possible implication of this new source of catecholamines, acting either as interneurons or as neuroendocrine cells, is discussed in the light of a local regulatory mechanism for islet secretion.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 28 (1985), S. 574-578 
    ISSN: 1432-0428
    Keywords: Glucagon ; diabetes ; noradrenaline ; insulin ; fructose-2,6-bisphosphate ; cyclic AMP-dependent protein kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent advances in the understanding of glucagoninsulin relationships at the level of the islets of Langerhans and of hepatic fuel metabolism are reviewed and their impact on our understanding of glucagon physiology and pathophysiology is considered. It now appears that α cells can respond directly to hyperglycaemia in the absence of insulin and β cells, but that antecedent hyperglycaemia masks or attenuates this response. Insulin appears to exert ongoing release inhibition upon glucagon secretion, probably via the intra-islet microvascular system that connects β cells to α cells. Diabetic hyperglucagonemia in insulin deficient states appears to be secondary to lack of the restraining influence of insulin. The α cell response to glucopenia, by contrast, may be in large part mediated by release of noradrenaline from nerve endings in contact with α cells. Glucagon's action on glucose and ketone production by hepatocytes is mediated by increase in cyclic-AMP-dependent protein kinase. The opposing action of insulin upon glucagon-mediated events probably occurs largely at this level. Consequently, when glucagon secretion or action is blocked, cyclic-AMP-dependent protein kinase activity is low even in the absence of insulin, explaining why marked glucose and ketone production is absent in bihormonal deficiency states.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: A-cell ; diabetes ; insulin ; plasma ; glucagon response to glucose and insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary These experiments were designed to determine whether the abnormal glucagon response of diabetics to a glucose meal can be restored to normal by the short-term administration of exogenous insulin in amounts sufficient to produce normal and above normal plasma insulin levels. The immunoreactive glucagon (IRG) response of nine nondiabetics to oral glucose was compared with that of ten juvenile and ten adult type diabetics. In the absence of exogenous insulin, the IRG response of diabetics was strikingly different from the nondiabetics, rising paradoxically, whereas in nondiabetics there was a decline in IRG. When plasma insulin levels were raised to normal by infusion of insulin (0.06 U/kg for 2 hr), the abnormal IRG response of adult type diabetics was not improved; the IRG response of the juvenile type patients was improved, but remained abnormal. Raising plasma insulin briefly to greater than normal concentrations inproved the IRG response during the glucose meal in both groups, but in the adult group total IRG suppression was still only half that of the nondiabetics; in the juvenile type group it was reduced to the nondiabetic level, but at glucose and insulin levels far above those of nondiabetics. The results are compatible with the view that the glucose-sensing function of the A-cells is, at least in part, mediated by or requires insulin. In juvenile diabetics, the abnormality is corrected by raising plasma insulin to above normal levels; adult onset diabetics appear to be less sensitive even to large doses of insulin during a carbohydrate load.
    Type of Medium: Electronic Resource
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