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  • 1
    ISSN: 1432-0428
    Keywords: Enkephalins ; morphine ; insulin secretion ; isolated rat islets ; islet perifusion ; diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The direct effects of an enkephalin analogue, (D-Ala2/MePhe4/Met/(O)-ol) enkephalin (DAMME), on insulin release from isolated islets of Langerhans of the rat have been investigated. DAMME had a dose-dependent effect on insulin secretion: low concentrations (10−10 to 10−8 mol/l) were stimulatory while high concentrations (10−5mol/l) were inhibitory in the presence of 8 mmol/l glucose. Similar effects were found with met-enkephalin, and with the longer acting alanine substituted metenkephalin. Morphine sulphate (5 sx 10−7 mol/l) also stimulated insulin release. The effects of enkephalin and morphine were blocked by the specific opiate antagonist naloxone hydrochloride (1.2 × 10−6 mol/l). The insulin secretory response of perifused islets to enkephalins and morphine was rapid, corresponding to the first phase of glucose induced insulin release. These observations suggest that there may be opiate receptors in islets, and that opioid peptides could modulate insulin release.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 16 (1979), S. 139-139 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Chlorpropamide-alcohol flush ; retinopathy ; glucose tolerance test ; serum insulin ; serum triglycerides ; blood metabolites ; Type 2 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum insulin and blood metabolite responses to oral glucose with and without intravenous naloxone were measured in 24 chlorpropamide-alcohol flush positive and negative Type 2 (non-insulin dependent) diabetic patients with and without retinopathy. In the chlorpropamide-alcohol flush positive patients with retinopathy, fasting blood glucose was increased 〉40% and the serum triglycerides were increased over twofold compared with each of the other three groups. Following oral glucose (50 g), the chlorpropamide-alcohol flush positive diabetic patients with complications had a lower serum insulin and higher blood glycerol than the other three groups. Thus, chlorpropamide-alcohol flush positive subjects with retinopathy showed distinct metabolic differences from the other three groups. There was no evidence that opiate-receptors influenced the metabolic response to oral glucose in the Type 2 diabetic patients since the infusion of intravenous naloxone produced no effect on the serum insulin or blood metabolites.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 18 (1980), S. 82-82 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 23 (1982), S. 460-460 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 17 (1979), S. 333-343 
    ISSN: 1432-0428
    Keywords: Genetics ; identical twins ; chlorpropamide alcohol flushing ; retinopathy ; enkephalin ; piqûre ; insulin dependent diabetes ; non-insulin dependent diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin dependent (IDD) and non-insulin dependent diabetes (NIDD) are separate disorders. Twin studies show that IDD cannot be entirely due to genetic causes as concordance is no more than about 50%, but there is some inherited predisposition to it as shown by HLA patterns. NIDD, on the other hand, is predominantly due to genetic causes since identical twins are nearly always concordant. Many cases of NIDD show chlorpropamide alcohol flushing (CPAF), a dominantly inherited feature which may precede the appearance of diabetes and thus act as a genetic marker for this type of diabetes. Diabetics who show chlorpropamide acohol flushing are less likely to develop retinopathy than those who do not. Genetic factors must therefore affect the incidence and severity of diabetic retinopathy. Chlorpropamide alcohol flushing is due to sensitivity to enkephalin. Enkephalin and other opioids affect carbohydrate metabolism and insulin release. It is possible therefore that they act as neurotransmitters and cause NIDD by a sympathetically mediated effect on the liver and pancreas — in other words, that as far as NIDD is concerned Claude Bernard's views on the cause of diabetes may have been right.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Identical twins ; Type 1 (insulin-dependent) diabetes mellitus ; intravenous glucose ; insulin response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To define the glucose to insulin dose-response relationship before the onset of diabetes, we studied 22 nondiabetic co-twins of patients with Type 1 (insulin-dependent) diabetes mellitus and nine control subjects. All had intravenous glucose tests at 0.02, 0.1 and 0.5 g/kg and were followedup prospectively for at least 6 years. Seven twins developed diabetes a mean of 7 months later; the remaining 15 are now unlikely to develop diabetes. The seven pre-diabetic twins had higher fasting insulin levels than control subjects (4.2±2.0 vs 1.8±1.8 nmol/l; p〈0.05); but lower glucose clearance (1.0±0.5 vs 1.9±0.7 %/min; p〈0.05), first phase insulin response at 0.5 g/kg (21.1±23.2 vs 143±50 nmol/l; p〈0.0001), and total insulin responses at 0.1 g/kg (p〈0.05) and 0.5 g/kg (p〈0.00005). Using a curve-fitting programme, the normal glucose to insulin relationship was lost in prediabetic twins who had lower coefficient of determination (R2) than control subjects (p〈0.01). In contrast, 15 low-risk twins and their nine control subjects had similar fasting glucose and insulin levels, glucose clearance, R2 and insulin secretory responses to different glucose loads. The positive predictive values of subnormal R2 and subnormal first phase insulin response were 67 % and 58 % respectively. These observations demonstrate an altered glucose to insulin dose-response relationship and loss of maximum insulin secretory response to glucose before the onset of Type 1 diabetes.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Impaired glucose tolerance ; pre-diabetes ; insulin-dependent diabetes ; identical twins ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Non-diabetic identical twins of insulin-dependent diabetic patients were studied within five years of the diagnosis of their index twin in order to determine whether changes in intermediary metabolism precede the onset of insulin-dependent diabetes mellitus. Two studies were performed: a cross-sectional study of 12 non-diabetic twins and a prospective study of a separate group of 41 non-diabetic twins. Ofthe 12 twins tested in the cross-sectional study six developed insulin-dependent diabetes and six did not; the six who developed diabetes were given an oral glucose load a mean of 10 months before diagnosis; they then had normal fasting blood glucose levels but worse glucose tolerance than control subjects (120 min post-load (mean±SD) blood glucose 8.5±3.5 vs 4.9±0.9 mmol/l respectively, p〈0.05). However, blood lactate, pyruvate, alanine, glycerol, 3-hydroxybutyrate and serum insulin levels were similar. In contrast, the six twins in this cross-sectional study who did not develop diabetes and are now unlikely to do so, as a group, had no significant changes compared with the control subjects though one had impaired glucose tolerance. To determine the predictive value of impaired glucose tolerance a separate group of 41 non-diabetic twins was studied prospectively for 8 to 22 years having a total of 147 glucose tolerance tests in this period; in this group six developed diabetes. Eight of the 41 had impaired glucose tolerance; impaired glucose tolerance was found in four of the six who developed diabetes as compared with only four of the 35 who did not (p〈0.01). Impaired glucose tolerance in these non-diabetic identical twins had a positive predictive value of33% for developing diabetes. The four twins with impaired glucose tolerance who remain nondiabetic now have normal glucose tolerance. We conclude that impaired glucose tolerance may precede the onset of insulin-dependent diabetes mellitus by many months but the change does not specifically predict the disease even in identical twins of diabetic patients. These observations are consistent with the possibility that in some twins the disease process can occur yet remit without leading to diabetes.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 33 (1990), S. 577-577 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: B-cell responses ; i.v. glucose ; i.v. glucagon ; nondiabetic twins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The B-cells of patients with recently diagnosed Type 1 (insulin-dependent) diabetes may have no response to glucose when the response to glucagon is present but attenuated. This observation suggests that the recognition of glucose is more severely affected than that for non-glucose stimulants. To determine whether a similar selective decrease in glucose response was present before the onset of diabetes we studied two groups of non-diabetic identical twins of patients with recently diagnosed Type 1 diabetes: one group with complement-fixing islet cell antibodies who were at high risk of developing diabetes (four of the five have already developed diabetes) and a group without such antibodies at low risk of developing diabetes. In addition, a group of patients with chronic pancreatitis were studied to control for non-specific damage to the B-cell. Responses to i. v. glucose and i.v. glucagon were compared. Patients with chronic pancreatitis has similar responses to both glucose and glucagon and the responses did not differ from control subjects. The B-cells of the immune positive group showed evidence of pathology because the insulin and C-peptide responses to both stimuli were reduced when compared to either their control subjects or the immune negative twin group. However, the B-cell response to both glucose and glucagon in the immune positive twins was similar. Because the B-cell response to glucose was not less than that to glucagon, a selective destruction of the glucose recognition system cannot be a characteristic of all twins throughout the period before they develop Type 1 diabetes.
    Type of Medium: Electronic Resource
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