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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 30 (1987), S. 354-359 
    ISSN: 1432-0428
    Keywords: CGRP ; nerve tissue proteins ; insulin secretion ; glucagon secretion ; somatostatin secretion ; in vivo ; pigs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Calcitonin gene-related peptide occurs in intrapancreatic nerves and endocrine cells. The peptide is therefore a candidate for being of physiological importance for pancreatic function. We examined the direct effects of calcitonin gene-related peptide on islet hormone secretion in the pig by infusing the peptide into the superior pancreatic artery. We found that 15 min intrapancreatic infusion of calcitonin gene-related peptide (22 pmol/min) decreased baseline pancreatic insulin output from 48±10 μU/min to 8±7μU/min (p〈0.01). Moreover, calcitonin gene-related peptide inhibited glucose-induced insulin secretion by 45% compared to controls (p〈0.01), yet left terbutaline (β2-adrenoceptor)-stimulated insulin secretion unaffected. Furthermore, while being without effect on baseline glucagon output, calcitonin gene-related peptide potentiated terbutaline-induced glucagon secretion more than seven-fold (p〈0.001). In contrast, the peptide did not affect baseline or stimulated pancreatic somatostatin output. We conclude that in pigs calcitonin gene-related peptide inhibits insulin secretion and potentiates glucagon secretion by direct effects on the pancreas that are not mediated by primary alterations in pancreatic somatostatin secretion. We suggest that the neuropeptide calcitonin gene-related peptide might be of importance for the intrapancreatic regulation of insulin and glucagon secretion in pigs.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Insulin secretion ; glucagon secretion ; islet function ; insulin sensitivity ; dexamethasone.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To establish whether islet compensation to deterioration of insulin action depends on inherent insulin sensitivity. Methods. We examined insulin and glucagon secretion after iv arginine (5 g) at fasting, 14 and greater than 25 mmol/l glucose concentrations before and after lowering of insulin sensitivity by oral dexamethasone (3 mg twice daily for 2 1/2 days) in 10 women with normal glucose tolerance, aged 58 or 59 years. Five women had high insulin sensitivity as shown by euglycaemic, hyperinsulinaemic clamp (99 ± 12 nmol glucose · kg body weight–1· min–1/pmol insulin · l–1; means ± SD) whereas five women had low insulin sensitivity (34 ± 15 nmol glucose · kg body weight–1· min–1/pmol insulin · l–1). Results. Dexamethasone reduced insulin sensitivity in both groups. Fasting insulin concentration increased by dexamethasone in high insulin sensitivity (72 ± 10 vs 49 ± 9 pmol/l, p = 0.043) but not in low insulin sensitivity (148 ± 63 vs 145 ± 78 pmol/l) whereas the fasting glucose concentration increased in low insulin sensitivity (6.5 ± 0.8 vs 5.8 ± 0.6 mmol/l, p = 0.043) but not in high insulin sensitivity (5.3 ± 0.8 vs 5.3 ± 0.6 mmol/l). Fasting glucagon concentration was not changed. Plasma insulin concentrations after raising glucose to 14 and more than 25 mmol/l and the insulin response to arginine at more than 25 mmol/l glucose were increased by dexamethasone in high insulin sensitivity (p 〈 0.05) but not changed by dexamethasone in low insulin sensitivity. Furthermore, in high but not in low insulin sensitivity, dexamethasone reduced the glucagon response to arginine (p = 0.043). Conclusion/interpretation. The results show that adaptation in islets function to dexamethasone-induced short-term reduction in insulin sensitivity is lacking in subjects with low inherent insulin sensitivity. [Diabetologia (1999) 42: 936–943]
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 20 (1981), S. 54-59 
    ISSN: 1432-0428
    Keywords: VIP ; secretin ; gastrin ; basal insulin secretion ; stimulated insulin secretion ; cholinergic stimulation ; β-adrenergic stimulation ; glucose stimulation ; in vivo ; mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The in vivo effects of vasoactive intestinal polypeptide (VIP), secretin and two different molecular forms of gastrin, gastrin 17 and pentagastrin, on basal and stimulated insulin secretion have been investigated in the mouse. All these peptides induced a moderate dose-dependent increase in basal insulin secretion. The different polypeptides showed complex effects on insulin release stimulated by glucose, the cholinergic agonist carbachol or the β adrenergic agonist L-isopropylnoradrenaline (LIPNA), these effects being dependent on the nature of the secretagogue. VIP and secretin both potentiated glucose-induced insulin release. Secretin inhibited insulin secretion induced by carbachol and LIPNA, whereas VIP potentiated L-IPNA-induced insulin secretion and had no influence on the effect of carbachol. Gastrin 17 and pentagastrin did not affect glucose- or carbachol-induced insulin release, whereas they inhibited L-IPNA-induced insulin secretion. The results suggest that VIP, secretin and gastrin display their effects on insulin secretion through different mechanisms. The results indirectly suggest the existence of separate insulin secretory pathways which operate differently, or at least partly differently, after glucose stimulation, cholinergic stimulation, and β-adrenergic stimulation.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 21 (1981), S. 54-59 
    ISSN: 1432-0428
    Keywords: VIP ; secretin ; gastrin ; basal insulin secretion ; stimulated insulin secretion ; cholinergic stimulation ; β-adrenergic stimulation ; glucose stimulation ; in vivo ; mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The in vivo effects of vasoactive intestinal polypeptide (VIP), secretin and two different molecular forms of gastrin, gastrin 17 and pentagastrin, on basal and stimulated insulin secretion have been investigated in the mouse. All these peptides induced a moderate dose-dependent increase in basal insulin secretion. The different polypeptides showed complex effects on insulin release stimulated by glucose, the cholinergic agonist carbachol or theβ-adrenergic agonist L-isopropylnoradrenaline (L-IPNA), these effects being dependent on the nature of the secretagogue. VIP and secretin both potentiated glucose-induced insulin release. Secretin inhibited insulin secretion induced by carbachol and L-IPNA, whereas VIP potentiated L-IPNA-induced insulin secretion and had no influence on the effect of carbachol. Gastrin 17 and pentagastrin did not affect glucose- or carbachol-induced insulin release, whereas they inhibited L-IPNA-induced insulin secretion. The results suggest that VIP, secretin and gastrin display their effects on insulin secretion through different mechanisms. The results indirectly suggest the existence of separate insulin secretory pathways which operate differently, or at least partly differently, after glucose stimulation, cholinergic stimulation, andβ-adrenergic stimulation.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Insulin secretion ; glucagon secretion ; islet function ; impaired glucose tolerance ; non-insulin-dependent diabetes mellitus ; pathogenesis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the islet adaptation to reduced insulin sensitivity in normal and glucose intolerant post-menopausal women, we performed a euglycaemic, hyperinsulinaemic clamp in 108 randomly selected women, aged 58–59 years. Of the 20 women with the lowest insulin sensitivity, 11 had impaired glucose tolerance (IGT) whereas 9 had normal glucose tolerance (NGT). These women together with 15 women with medium insulin sensitivity and 16 women with high insulin sensitivity and NGT were further examined with arginine stimulation at three glucose levels (fasting, 14 and 〉 25 mmol/l). In NGT, the acute insulin response (AIR) to 5 g i. v. arginine at all three glucose levels and the slopeAIR, i. e. the glucose potentiation of insulin secretion, were markedly increased in the women with the lowest insulin sensitivity and NGT compared to those with medium or high insulin sensitivity. In contrast, in low insulin sensitivity, AIR was significantly lower in IGT than in NGT (at glucose 14 mmol/l p = 0.015, and at 〉 25 mmol/ l p = 0.048). The potentiation of AIR induced by low insulin sensitivity in women with NGT was reduced by 74 % (AIR at 14 mmol/l glucose) and 57 % (AIR at 〉 25 mmol/l glucose), respectively, in women with IGT. Also the slopeAIR was lower in IGT than in NGT (p = 0.025); the increase in slopeAIR due to low insulin sensitivity was abolished in IGT. In contrast, glucagon secretion was not different between women with IGT as opposed to NGT. We conclude that as long as there is an adequate beta-cell adaptation to low insulin sensitivity with increased insulin secretory capacity and glucose potentiation of insulin secretion, NGT persists. [Diabetologia (1996) 39: 1099–1107]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Insulin secretion ; glucagon secretion ; islet function ; impaired glucose tolerance ; non-insulin-dependent diabetes mellitus ; pathogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the islet adaptation to reduced insulin sensitivity in normal and glucose intolerant post-menopausal women, we performed a euglycaemic, hyperinsulinaemic clamp in 108 randomly selected women, aged 58–59 years. Of the 20 women with the lowest insulin sensitivity, 11 had impaired glucose tolerance (IGT) whereas 9 had normal glucose tolerance (NGT). These women together with 15 women with medium insulin sensitivity and 16 women with high insulin sensitivity and NGT were further examined with arginine stimulation at three glucose levels (fasting, 14 and 〉25 mmol/l). In NGT, the acute insulin response (AIR) to 5 g i. v. arginine at all three glucose levels and the slopeAIR, i. e. the glucose potentiation of insulin secretion, were markedly increased in the women with the lowest insulin sensitivity and NGT compared to those with medium or high insulin sensitivity. In contrast, in low insulin sensitivity, AIR was significantly lower in IGT than in NGT (at glucose 14 mmol/l p=0.015, and at 〉25 mmol/l p=0.048). The potentiation of AIR induced by low insulin sensitivity in women with NGT was reduced by 74% (AIR at 14 mmol/l glucose) and 57% (AIR at 〉25 mmol/l glucose), respectively, in women with IGT. Also the slopeAIR was lower in IGT than in NGT (p=0.025); the increase in slopeAIR due to low insulin sensitivity was abolished in IGT. In contrast, glucagon secretion was not different between women with IGT as opposed to NGT. We conclude that as long as there is an adequate beta-cell adaptation to low insulin sensitivity with increased insulin secretory capacity and glucose potentiation of insulin secretion, NGT persists.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Keywords Islet function ; arginine ; insulin secretion ; glucagon secretion ; reproducibility ; coefficient of variation ; priming effect.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Quantitative determination of insulin secretion is of importance both clinically and in research. The optimal method has not been established, although several different methods have been used. We determined the reproducibility of islet function parameters obtained by the glucose-dependent arginine stimulation test, and also studied the priming effect of arginine on subsequent acute insulin responses. The test measures the acute insulin (AIR) and glucagon (AGR) responses to i. v. arginine (5 g injected over 45 s) at fasting glucose and glucose concentrations clamped at 14 and above 25 mmol/l, as well as the glucose potentiation of insulin secretion (slopeAIR) and the glucose inhibition of glucagon secretion (slopeAGR). When the test was performed twice in seven healthy women (mean ± SD age 58.7 ± 0.5 years, BMI 27.6 ± 5.5 kg/m2), the AIRs to arginine had a within-subject coefficient of variation (CV) of 18.6 % at fasting glucose, 18.7 % at 14 mmol/l glucose and 16.3 % at above 25 mmol/l glucose. The CVs for AGR were 11.6, 14.9 and 8.9 %, respectively. The CV of the slopeAIR was 24 % and of the slopeAGR 17.2 %. The arginine priming study was performed in six healthy women (age 63.7 ± 0.3 years, BMI 28.0 ± 6.9 kg/m2). Saline or arginine (5 g) was injected at fasting glucose, followed by arginine (5 g) at 14 mmol/l glucose. There was no difference between the acute insulin or glucagon responses to arginine at 14 mmol/l glucose in the two conditions, suggesting that there is no priming effect of arginine on the subsequent acute insulin or glucagon responses. Therefore, this method is a good tool to determine insulin secretion as, apart from its good reproducibility, it also provides several important parameters of islet function. [Diabetologia (1998) 41: 772–777]
    Type of Medium: Electronic Resource
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