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  • 1
    Electronic Resource
    Electronic Resource
    Glycation of glucagon-like peptide-1(7–36)amide: characterization and impaired action on rat insulin secreting cells (1998)
    Springer
    Diabetologia 41 (1998), S. 1187-1193 
    Details
    ISSN: 1432-0428
    Keywords: Keywords GLP-1(7 ; 36)amide ; glycation ; insulin secretion ; BRIN-BD11 cells.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucagon-like peptide-1(7–36)amide (truncated GLP-1, tGLP-1) is a potent insulin releasing hormone of the enteroinsular axis. This study has examined glycation of tGLP-1 and effects of such structural modification on insulin secretion. Monoglycated tGLP-1 (Mr 3463.8, determined by plasma desorption mass spectrometry) was prepared by incubation with glucose under reducing conditions and purified by reversed-phase high performance liquid chromatography. Automated Edman degradation indicated that tGLP-1 was specifically glycated at the amino terminal His7 site. In extracts from mouse small intestine, glycated tGLP-1 represented approximately 14 % of the total tGLP-1 content. Effects of glycated and non-glycated tGLP-1 on insulin secretion were examined using glucose-responsive clonal BRIN-BD11 cells. In acute (20 min) incubations, 10–9 mol/l tGLP-1 enhanced insulin release by 2.2-fold and 1.5-fold at 5.6 and 11.1 mmol/l glucose, respectively. In contrast, 10–9 mol/l glycated tGLP-1 failed to stimulate secretion and insulin output was decreased by 34–73 % following glycation. At 5.6 mmol/l glucose, non-glycated tGLP-1 (3 × 10–10 mol/l–10–8 mol/l) exerted a 2.3-fold to 3.2-fold increase in insulin secretion compared with controls. The effect of glycated tGLP-1 at 10–9 mol/l and 3 × 10–9 mol/l was reduced by 51–55 % compared with non-glycated peptide, and its insulinotropic action was effectively abolished. These data indicate that when tGLP-1 is glycated at the amino terminal His7, this modification substantially reduces the glucose-dependent insulinotropic action of the peptide. [Diabetologia (1998) 41: 1187–1193]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051050
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  • 2
    Electronic Resource
    Electronic Resource
    Metabolic activation of chemical carcinogens by hepatic preparations from streptozotocin-treated rats (1989)
    Springer
    Diabetologia 32 (1989), S. 135-139 
    Details
    ISSN: 1432-0428
    Keywords: Metabolic activation ; insulin-dependent diabetes ; chemical carcinogens ; Ames test ; aromatic amines ; polycyclic aromatic hydrocarbons ; food mutagens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of insulin-dependent diabetes on the hepatic microsomal activation of chemical carcinogens to mutagenic intermediates in the Ames test was investigated in rats pretreated with streptozotocin. In order to discern between the effects of streptozotocin itself and that of the resulting diabetes, groups of streptozotocin-treated rats received either nicotinamide simultaneously with the diabetogenic agent to prevent the onset of diabetes or daily treatment with insulin in order to antagonise the effects of diabetes. The activation of two nitrosamines, nitrosopiperidine and nitrosopyrrolidine was markedly increased following treatment of the animals with streptozotocin, the effect being preventable by nicotinamide and effectively antagonised by insulin. A similar increase in mutagenic response was also seen when Glu-P-1, a carcinogen generated during the cooking of proteinaceous food, was employed as the mutagen. In contrast, the diabetic rats were less efficient than control animals in activating the aromatic amine 2-aminofluorene to mutagenic intermediates. Concomitant administration of nicotinamide with streptozotocin prevented the decrease in mutagenicity, and daily treatment of diabetic rats with insulin partially restored mutagenic response to control levels. Streptozotocin-induced diabetes had no effect on the mutagenicity of 4-aminobiphenyl and the two polycyclic aromatic hydrocarbons, benzo(a)pyrene and 3-methylcholanthrene. The present findings clearly illustrate that diabetes modulates the metabolic activation of carcinogenic chemicals, the effect being dependent on the nature of the carcinogen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00505186
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  • 3
    Electronic Resource
    Electronic Resource
    Influence of a transplantable insulinoma on the pancreatic status of insulin and pancreatic polypeptide in the rat (1985)
    Springer
    Diabetologia 28 (1985), S. 157-160 
    Details
    ISSN: 1432-0428
    Keywords: Transplantable insulinoma ; islet cell tumour ; insulin ; pancreatic polypeptide ; radioimmunoassay ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of endogenous hyperinsulinaemia, produced by syngeneic transplantation of rat insulinoma at an extrapancreatic site, on pancreatic insulin and pancreatic polypeptide has been examined by radioimmunoassay and immunohistochemistry. Twenty days after subcutaneous transplantation, tumour-bearing rats exhibited marked hyperinsulinaemia and hypoglycaemia, with plasma pancreatic polypeptide concentrations similar to controls. Immunoreactive insulin levels in the head and tail of pancreas of tumour-bearing rats were reduced by 90–95% compared with control animals. Immunoreactive pancreatic polypeptide levels in the head of the pancreas were reduced by 70%, but the relatively low levels of peptide in the pancreatic tail were similar in tumour-bearing and control rats. Insulin and pancreatic polypeptide cells were weakly immunofluorescent in tumour-bearing rat pancreas. In conclusion, the presence of an insulinoma at an extrapancreatic site resulted in a severe depletion of endogenous insulin and pancreatic polypeptide, suggesting that there is a functional relationship between the beta and pancreatic polypeptide cell.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00273864
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  • 4
    Electronic Resource
    Electronic Resource
    Abnormal plasma glucose and insulin responses in heterozygous lean (ob/+) mice (1981)
    Springer
    Diabetologia 20 (1981), S. 573-577 
    Details
    ISSN: 1432-0428
    Keywords: Expression of ob gene ; glucose tolerance ; insulin secretion ; insulin sensitivity ; ob/+ mice ; obese hyperglycaemic syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the effect of the ob gene in the heterozygous condition, plasma glucose and insulin responses of adult heterozygous lean (ob/+) mice were compared with mice of the homozygous lean (+/+) and homozygous obese (ob/ob) genotypes. The ob/+ mice consumed 24% more food than +/+ mice although body weights were similar. Plasma glucose and insulin concentrations were respectively 16% and 176% higher in ob/+ mice than +/+ mice in the freely fed state, and 44% and 88% higher during glucose tolerance tests. In 24 hour fasted ob/+ mice, plasma glucose concentrations were 23% higher than +/+ mice but plasma insulin concentrations were not significantly different. Arginine produced a greater insulin response (172%) and a greater fall in glycaemia (200%) in ob/ + mice. A significant difference in the hypoglycaemic effect of insulin in ob/+ and +/+ mice was not observed. These results demonstrate an effect of the ob gene on glucose homeostasis in heterozygous lean (ob/+) mice. The abnormalities were qualitatively similar but considerably less severe than those in ob/ob mice, suggesting that ob/+ mice might prove useful to study factors predisposing to inappropriate hyperglycaemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00252768
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  • 5
    Electronic Resource
    Electronic Resource
    Engineering cultured insulin-secreting pancreatic B-cell lines (1999)
    Springer
    Journal of molecular medicine 77 (1999), S. 235-243 
    Details
    ISSN: 1432-1440
    Keywords: Key words Insulin-secreting cell lines ; Clonal pancreatic B-cells ; Insulin secretion ; Electrofusion ; Molecular engineering
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Despite many triumphs, a significant limitation of the usefulness of many of the available B-cell lines for the study of insulin secretion are either inappropriate or lack of responsiveness to glucose. Commonly employed cell lines generated prior to the 1990s following X-ray irradiation (RINm5F cells) or simian virus 40 B-cell transformation (HIT-T15 cells and BTC) fall into this category. More recent success has been achieved with the generation of INS-1 cells and MIN6 cells, but the production of these cell lines owes much to good fortune, dedication and hard work. In the present era, molecular biology techniques provide the opportunity to engineer novel pancreatic B-cell lines which possess many attributes of normal insulin-secreting cells. This review describes the electrofusion of normal NEDH rat pancreatic B-cells with immortal RINm5F cells to create three new glucose-responsive clonal insulin-secreting cells, designated BRIN-BG5, BRIN-BG7 and BRIN-BD11. These cell lines exhibit up to four-fold insulin-secretory responses to depolarization with 25 mmol/l K+, 7.68 mmol/l Ca2+, 10 mmol/l l-alanine, and activation of protein kinase C or adenylate cyclase with 10 nmol/l phorbol-12-myristate-13-acetate or 25 μmol/l forskolin, respectively. The maximal insulin-secretory response of both BRIN-BG5 and BRIN-BG7 cells to glucose occurred at 8.4 mmol/l (1.9- and 1.8-fold increases, respectively). In contrast, 4.2–16.7 mmol/l glucose evoked a stepwise 2- to 3-fold of insulin release from BRIN-BD11 cells. The superior glucose responsiveness of BRIN-BD11 cells compared with BRIN-BG5 or BRIN-BG7 cells was associated with increased expression of GLUT-2 and a greater contribution of glucokinase to total glucose phosphorylating enzyme activity. Furthermore, BRIN-BD11 cells also showed appropriate responses to a diverse range of modulators of pancreatic B-cell function, including amino acids, neurotransmitters and sulphonylurea drugs. Collectively these observations indicate that genetic modification of insulin-secreting cells by electrofusion (or transfection with cDNA) offers a new avenue for generation of useful clonal glucose-responsive pancreatic B-cell lines for studies of insulin secretion and transplantation in insulin-dependent diabetes mellitus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050344
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  • 6
    Electronic Resource
    Electronic Resource
    GIP and the enteroinsular axis in hyperinsulinaemic and hypoinsulinaemic diabetic mice
    Amsterdam : Elsevier
    Regulatory Peptides 13 (1985), S. 90 
    Details
    ISSN: 0167-0115
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0167-0115(85)90138-7
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  • 7
    Electronic Resource
    Electronic Resource
    Measurement of immunoreactive C-peptide to investigate the insulin secretion defect in aston ob/ob mice
    Amsterdam : Elsevier
    Regulatory Peptides 13 (1985), S. 100 
    Details
    ISSN: 0167-0115
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0167-0115(85)90157-0
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  • 8
    Electronic Resource
    Electronic Resource
    Effects of a transplantable insulinoma upon regulatory peptide concentrations in the gastrointestinal tract of the rat (1986)
    Springer
    Diabetologia 29 (1986), S. 334-338 
    Details
    ISSN: 1432-0428
    Keywords: Insulinoma ; substance P ; neurokinin A ; vasoactive intestinal polypeptide ; somatostatin ; gastrin-releasing peptide ; enteroglucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The rapid growth (0.8±0.3 g/day) of a transplantable insulinoma, which also contained substance P (2.9±2.3 pmol/g) and gastrin-releasing peptide (3.2± 2.1 pmoll/g), resulted in the development of hyperphagia, hyperinsulinaeinia and hypoglycaemia in rats (n=8). After a 14-day growth period, the insulinoma-bearing rats showed an increase (49%; p〈0.01) in the weight of the small intestine but no significant change in stomach weight compared with control animals. The content (pmol/organ) of somatostatin, substance P, neurokinin A and vasoactive intestinal peptide in the stomachs of the tumour rats was unchanged. A depletion in the content (53% p〈0.01) and concentration (57%; p〈0.01) of gastrin-releasing peptide, however, suggested either hypersecretion, possibly mediated through hypoglycaemia-induced vagal stimulation, or inhibition of synthesis. The concentration and content of glucagon-like immunoreactivity (enteroglucagon) in the small intestine of the insulinoma rats increased markedly (47%; p〈0.01 and 120%; p〈0.01). This increase is consistent with a proposed role of this peptide as a factor trophic to the intestinal mucosa. No significant changes in the concentrations of somatostatin, substance P, neurokinin A, vasoactive intestinal peptide and gastrin-releasing peptide in the small intestine were observed. However, the increase in gut weight resulted in a greater content of vasoactive intestinal peptide (40%; p〈0.01) and substance P (37%; p〈0.05) in the insulinoma rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00452072
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  • 9
    Electronic Resource
    Electronic Resource
    Increased responsiveness to glucoregulatory effect of opiates in obese-diabetic ob/ob mice (1987)
    Springer
    Diabetologia 30 (1987), S. 33-37 
    Details
    ISSN: 1432-0428
    Keywords: Opiates ; enkephalin analogues ; naloxone ; obesediabetic ob/ob mice ; glucose ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma glucose and insulin responses to opiate receptor stimulation and antagonism were determined in 12–14 week old lean and obese-diabetic Aston ob/ob mice. The opiate receptor antagonist naloxone (1 mg/kg intraperitoneally) rapidly and transiently raised glucose and suppressed insulin concentrations in lean mice, and produced qualitatively similar but more protracted responses in ob/ob mice. Selective stimulation of μ- and δ-opiate receptors using the enkephalin analogues Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH (1mg/kg, intraperitoneally) and Tyr-D-Ala-Gly-Phe-D-Leu (10 mg/kg intraperitoneally) respectively, rapidly and transiently increased glucose and insulin concentrations in lean and ob/ob mice. The ob/ob mice exhibited greater glucose and insulin responses to these analogues. The results (1) provide evidence that endogenous opiates participate in the regulation of glucose and insulin homeostasis, and (2) suggest that increased responsiveness to μ- and δ-opiate receptor stimulation may contribute to the hyperglycaemia and hyperinsulinaemia of obese-diabetic mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01788904
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  • 10
    Electronic Resource
    Electronic Resource
    Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice (1990)
    Springer
    Diabetologia 33 (1990), S. 462-464 
    Details
    ISSN: 1432-0428
    Keywords: Antihyperglycaemic plants ; glucose homeostasis ; traditional treatments for diabetes ; streptozotocin-diabetic mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects on glucose homeostasis of eleven plants used as traditional treatments for diabetes mellitus were evaluated in normal and streptozotocin diabetic mice. Dried leaves of agrimony (Agrimonia eupatoria), alfalfa (Medicago saliva), blackberry (Rubus fructicosus), celandine (Chelidonium majus), eucalyptus (Eucalyptus globulus), lady's mantle (Alchemilla vulgaris), and lily of the valley (Convallaria majalis); seeds of coriander (Coriandrum sativum); dried berries of juniper (Juniperus communis); bulbs of garlic (Allium sativum) and roots of liquorice (Glycyrhizza glabra) were studied. Each plant material was supplied in the diet (6.25% by weight) and some plants were additionally supplied as decoctions or infusions (1 g/400 ml) in place of drinking water to coincide with the traditional method of preparation. Food and fluid intake, body weight gain, plasma glucose and insulin concentrations in normal mice were not altered by 12 days of treatment with any of the plants. After administration of streptozotocin (200 mg/kg i.p.) on day 12 the development of hyperphagia, polydipsia, body weight loss, hyperglycaemia and hypoinsulinaemia were not affected by blackberry, celandine, lady's mantle or lily of the valley. Garlic and liquorice reduced the hyperphagia and polydipsia but did not significantly alter the hyperglycaemia or hypoinsulinaemia. Treatment with agrimony, alfalfa, coriander, eucalyptus and juniper reduced the level of hyperglycaemia during the development of streptozotocin diabetes. This was associated with reduced polydipsia (except coriander) and a reduced rate of body weight loss (except agrimony). Alfalfa initially countered the hypoinsulinaemic effect of streptozotocin, but the other treatments did not affect the fall in plasma insulin. The results suggest that certain traditional plant treatments for diabetes, namely agrimony, alfalfa, coriander, eucalyptus and juniper, can retard the development of streptozotocin diabetes in mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00405106
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