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  • 1
    ISSN: 1432-0428
    Keywords: Pertussis vaccine ; islet activating protein ; insulin ; glucagon ; perfused pancreas ; spontaneous diabetic rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The early phase of insulin secretion to an oral glucose load was blunted in spontaneous diabetic rats. The blunted insulin secretion was associated with markedly impaired glucose tolerance. A single injection of the islet activating protein (IAP), a protein derived from the culture medium of Bordetella pertussis, into the spontaneous diabetic rats normalised glucose tolerance. The increase in insulin response to glucose was an important contributing factor to the improvement of glucose tolerance. This curative effect of the IAP on the diabetic state was of long duration; glucose tolerance remained virtually normal over a period of one month in the diabetic rats. Perfusion of the isolated pancreas of the diabetic rats pretreated with IAP showed an increase in insulin response to glucose and loss of suppression of glucagon secretion by noradrenaline.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: C-peptide ; diabetes mellitus ; insulin secretion ; MELAS ; mitochondrial gene mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent evidence suggests possible linkage between diabetes mellitus and mitochondrial gene mutation. We surveyed mitochondrial tRNALEU(UUR) (3243) mutation in 7 mitochondrial encephalomyopathy, lactic acidosis and stroke-like episode (MELAS) families and identified 24 mutated subjects (7 MELAS probands and 17 non-MELAS relatives) as well as 11 non-mutant family members. An OGTT in the 24 mutant relatives revealed 14 diabetic subjects, 3 with impaired glucose tolerance and 7 with normal glucose tolerance and all non-mutant family members as having normal glucose tolerance. Insulinogenic index was significantly reduced in the mutant diabetic subjects and those with impaired and normal glucose tolerance in comparison with the normal control subjects and the non-mutant members. Urinary 24-h C-peptide immunoreactivity excretion was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance, compared with the control subjects and the non-mutant family members. Plasma C-peptide immunoreactivity 6 min after glucagon injection was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance compared with the control subjects and the non-mutant family members. Si, an index of insulin sensitivity of the four mutant subjects was within normal range. Islet cell antibodies were negative in sera of eight mutated diabetic subjects, 2 and 6 with impaired and normal glucose tolerance, respectively. Diabetic retinopathy and nephropathy were demonstrated in 7 (50%) and 12 (85.7%) of 14 mutant diabetic subjects, respectively. Neurosensory deafness was demonstrated in 12 (85.7%) of 14 mutated diabetic subjects, (66.7%) of 3 mutated impaired glucose tolerant subjects, but not detected in 6 mutated normal glucose tolerant subjects and 11 non-mutant family members. These findings suggest that the tRNALEU(UUR) mutation is associated with pancreatic beta-cell secretory defect of insulin.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Keywords N-acetylcysteine ; glutathione ; tumour necrosis factor α ; diabetic neuropathy ; motor nerve conduction velocity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor α (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NAC-treated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats. [Diabetologia (1996) 39: 263–269]
    Type of Medium: Electronic Resource
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  • 4
    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: Keywords Oxidative stress ; 8-oxo-2 ′-deoxyguanosine ; diabetic complication ; smoking.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Augmented oxidative stress induced by hyperglycaemia possibly contributes to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine to 8-oxo, 2 ′-deoxyguanosine in DNA. To investigate the possible contribution of oxidative DNA damage to the pathogenesis of diabetic complications, we measured the content of 8-oxo, 2 ′-deoxyguanosine in the urine and the blood mononuclear cells of Type II (non-insulin-dependent) diabetic patients. Methods. We studied 53 Type II diabetic patients and 39 age-matched healthy control subjects. We assayed 8-oxo, 2 ′-deoxyguanosine by HPLC-electrochemical detection method. Results. The content of 8-oxo, 2 ′-deoxyguanosine in the urine and the mononuclear cells of the Type II diabetic patients was much higher than that of the control subjects. Urinary 8-oxo, 2 ′-deoxyguanosine excretion and the 8-oxo, 2 ′-deoxyguanosine content in the mononuclear cells from the diabetic patients with complications were higher than those from the diabetic patients without complications. Urinary excretion of 8-oxo, 2 ′-deoxyguanosine was significantly correlated with the 8-oxo, 2 ′-deoxyguanosine content in the mononuclear cells. The 8-oxo, 2 ′-deoxyguanosine content in the urine and mononuclear cells was correlated with the haemoglobin A1 c value. Conclusion/interpretation. This is the first report of a direct association between oxidative DNA damage and the complications of diabetes. The augmented oxidative DNA damage in diabetes is speculated to contribute to the pathogenesis of diabetic complications. [Diabetologia (1999) 42: 995–998]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Key words C-peptide, diabetes mellitus, insulin secretion, MELAS, mitochondrial gene mutation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent evidence suggests possible linkage between diabetes mellitus and mitochondrial gene mutation. We surveyed mitochondrial tRNALEU(UUR) (3243) mutation in 7 mitochondrial encephalomyopathy, lactic acidosis and stroke-like episode (MELAS) families and identified 24 mutated subjects (7 MELAS probands and 17 non-MELAS relatives) as well as 11 non-mutant family members. An OGTT in the 24 mutant relatives revealed 14 diabetic subjects, 3 with impaired glucose tolerance and 7 with normal glucose tolerance and all non-mutant family members as having normal glucose tolerance. Insulinogenic index was significantly reduced in the mutant diabetic subjects and those with impaired and normal glucose tolerance in comparison with the normal control subjects and the non-mutant members. Urinary 24-h C-peptide immunoreactivity excretion was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance, compared with the control subjects and the non-mutant family members. Plasma C-peptide immunoreactivity 6 min after glucagon injection was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance compared with the control subjects and the non-mutant family members. Si, an index of insulin sensitivity of the four mutant subjects was within normal range. Islet cell antibodies were negative in sera of eight mutated diabetic subjects, 2 and 6 with impaired and normal glucose tolerance, respectively. Diabetic retinopathy and nephropathy were demonstrated in 7 (50 %) and 12 (85.7 %) of 14 mutant diabetic subjects, respectively. Neurosensory deafness was demonstrated in 12 (85.7 %) of 14 mutated diabetic subjects, (66.7 %) of 3 mutated impaired glucose tolerant subjects, but not detected in 6 mutated normal glucose tolerant subjects and 11 non-mutant family members. These findings suggest that the tRNALEU(UUR) mutation is associated with pancreatic beta-cell secretory defect of insulin. [Diabetologia (1994) 37: 818–825]
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: N-acetylcysteine ; glutathione ; tumour necrosis factor α ; diabetic neuropathy ; motor nerve conduction velocity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor α (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NAC-treated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Keywords Deafness ; mitochondrial DNA mutation ; insulin ; C-peptide ; lactate.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD. [Diabetologia (1998) 41: 584–588]
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Keywords Troglitazone ; diabetic neuropathy ; free radical scavenger ; tumour necrosis factor-α (TNF-α) ; motor nerve conduction velocity (MNCV).
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Free-radical scavengers and inhibitors of tumour necrosis factor-α (TNF-α) such as N-acetylcysteine and pentoxifylline have been shown to inhibit the development of peripheral neuropathy in streptozotocin(STZ)-induced diabetic rats. In this study we examined the effect of troglitazone, an anti-diabetic thiazolidinedione, on diabetic neuropathy, since it also is a free-radical scavenger and a TNF-α inhibitor. Rats were fed powder chow mixed with troglitazone at 0.5 % and 0.125 % ad libitum. Although blood glucose concentrations were remarkably higher and body weight lower in diabetic than in nondiabetic rats, troglitazone had no effect on these throughout the 24-week experiment. Serum lipoperoxide concentrations, tibial nerve lipoperoxide content and serum TNF-α activity induced by lipopolysaccharide was increased in diabetic rats, but inhibited in troglitazone-treated rats. Motor nerve conduction velocity (MNCV) of the tibial nerve slowed in diabetic rats, compared with that in nondiabetic rats. On the other hand, the slowed MNCV was (p 〈 0.05–0.01) inhibited after weeks 12 and 16 of the experiment in diabetic rats treated with high and low doses of troglitazone, respectively. Morphometric analysis showed that troglitazone suppressed the decrease of the myelinated fibre area (p 〈 0.05), axon/myelin ratio (p 〈 0.01) and fascicular area (p 〈 0.05) and suppressed the increase of myelinated fibre density (p 〈 0.001) in diabetic rats. These results indicate that troglitazone has a beneficial effect on peripheral neuropathy in STZ-induced diabetic rats irrespective of blood glucose concentrations. [Diabetologia (1998) 41: 1321–1326]
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0509
    Keywords: Key words: Paraduodenal hernia—MRI—CT—Internal hernia.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Paraduodenal hernias are rare congenital malformations. We report an unusual case of bilateral paraduodenal hernias diagnosed preoperatively by small bowel series, computed tomography (CT), and magnetic resonance imaging (MRI). Both CT and MRI are useful in the noninvasive diagnosis of paraduodenal hernias.
    Type of Medium: Electronic Resource
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