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  • 1
    Electronic Resource
    Electronic Resource
    Effects of exogenous hormones and glucose on plasma levels and hepatic metabolism of amino acids in the fetus and in the newborn rat (1976)
    Springer
    Diabetologia 12 (1976), S. 327-337 
    Details
    ISSN: 1432-0428
    Keywords: Plasma amino acids ; liver gluconeogenesis ; glucose ; insulin ; glucagon ; cortisol ; fetus ; newborn ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study examines the role of insulin, glucagon and cortisol in the regulation of gluconeogenesis from lactate and amino acids in fetal and newborn rats. Injection of glucagon in the fullterm fetal rat caused a rise in glucose (and insulin) and a fall in blood levels of most individual amino acids, stimulated hepatic accumulation of 14C-amino isobutyric acid and 14C-cycloleucine and increased the conversion of 14C lactate, alanine and serine to glucose in vivo and in vitro (liver slices). Such changes were equivalent to the changes seen in 4 h old newborn rats. When glucagon was administered at birth, little difference was observed between control and treated animals in plasma amino acids and a smaller increment in conversion of 14C substrate to glucose occurred. By contrast, insulin injection at birth caused hypoglycemia, suppression of levels of certain amino acids and inhibition of conversion of 14C substrates into glucose. Glucose injection at birth caused elevated glycemia and plasma insulin and suppression of most amino acid levels and of conversion of 14C substrate into glucose. Cortisol injection at birth caused a marked, generalized hyperaminoacidemia, a stimulation of glucagon secretion and of conversion of 14C substrates into glucose. These observations support the thesis that glucagon plays a major role in the induction of hepatic gluconeogenesis and that insulin acts as an antagonist hormone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00420976
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  • 2
    Electronic Resource
    Electronic Resource
    The metabolic and hormonal responses to glucose infusion in anaesthetized normal and diabetic dogs controlled by an artificial B-cell (1980)
    Springer
    Diabetologia 18 (1980), S. 479-485 
    Details
    ISSN: 1432-0428
    Keywords: Glucose ; artificial pancreas ; insulin ; glucagon ; lactate ; pyruvate ; alanine ; free fatty acids ; anaesthesia ; metabolic response ; insulin infusion ; diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolic response to glucose infusion in anaesthetized normal and pancreatectomized dogs has been assessed. Normoglycaemia was achieved in the diabetic dogs with an external artificial B-cell which administered insulin into the peripheral circulation. No differences were found in the levels of blood glucose, glucagon, lactate, pyruvate and plasma non-esterified fatty acids, either in the fasting state or in response to glucose infusion. However, compared to normal animals normoglycaemic diabetic dogs had significantly elevated circulating levels of insulin and alanine at all times. Fasting levels of the same hormones and metabolites were also measured in conscious dogs. Blood pyruvate levels were higher, and plasma non-esterified fatty acid levels lower, in the anaesthetized animals. There were also minor but consistent changes in blood glucose and plasma insulin while glucagon, lactate and alanine levels were unaffected by anaesthesia. In conclusion, controlled barbiturate anaesthesia has relatively minor effects on the metabolic and hormonal status of the dog. The metabolic and hormonal response to glucose infusion in pancreatectomized dogs treated with an artificial B-cell was almost entirely normalized, except for peripheral hyperinsulinaemia and hyperalaninaemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00261704
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  • 3
    Electronic Resource
    Electronic Resource
    Blood glucose control and insulin clearance in unrestrained diabetic dogs portally infused with a portable insulin delivery system (1980)
    Springer
    Diabetologia 19 (1980), S. 452-457 
    Details
    ISSN: 1432-0428
    Keywords: Glucose ; insulin ; infusion ; hepatic degradation ; insulin clearance ; portal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Long term glucose control in pancreatectomised dogs has been obtained with portal insulin therapy. When compared to a previous similar study using peripheral infusions, 20% less exogenous insulin was required and peripheral fasting insulin levels were 30% lower. Animals (n = 5) were unrestrained, conscious and carried a programmable insulin pump for 163–224 days. In the post-absorptive state blood glucose was normal (87±5 mg/dl) as was plasma insulin (10±1 mU/l) with porcine insulin infused at a basal rate of 0.36±0.01 mU/kg/min. Following ingestion of a standard mixed meal the infusion rate was increased to 2.47±0.09 mU/kg/ min for 7 1/2 h resulting in post-prandial normalisation of blood glucose. Peripheral plasma insulin levels were twice normal during the post-prandial infusion, but only half those previously reported with peripheral infusions. Insulin clearance rates were 37 ml/kg/min in the basal state and rose significantly post-prandially. In the absence of extra meal-time insulin the clearance rate was unaffected by the resulting post-prandial hyperglycaemia and similar to values observed with insulin infused peripherally at 0.45±0.03 mU/kg/min. No significant increase in the post-prandial rate of insulin clearance relative to the fasting rate was observed with peripherally administered insulin. It was thus concluded that portal insulin replacement in pancreatectomised dogs could normalise both blood glucose and insulin in the fasting state, but post-prandial peripheral insulin levels remained elevated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00281825
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  • 4
    Electronic Resource
    Electronic Resource
    Insulin and glucagon secretion in BB Wistar rats with impaired glucose tolerance (1983)
    Springer
    Diabetologia 24 (1983), S. 58-62 
    Details
    ISSN: 1432-0428
    Keywords: Type I diabetes ; BB rat ; impaired glucose tolerance ; animal model ; insulin ; glucagon ; insulitis ; glucose ; arginine ; tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucose tolerance and insulin secretion were studied in non-diabetic littermates (n=154) of BB diabetic rats, aged 4–6 months. Initial screening involved two intraperitoneal glucose tolerance tests (0.2g/100g body weight) performed one week apart. Nineteen rats (12%) were found to have impaired tolerance which persisted in 14 (74%) (group 1) and was transient in five animals (group 2). Seven rats progressed to overt diabetes in group 1, but none in group 2. Group 1 was characterized by (a) sustained abnormalities in glucose response to oral and intraperitoneal glucose, as well as intraperitoneal tolbutamide and arginine; (b) fasting hypoinsulinaemia; (c) decreased insulin response to glucose and tolbutamide; (d) suppression of the early and late phases of immunoreactive insulin response to intravenous glucose; (e) no systematic abnormalities in glucagon secretion; and (f) the presence of significant insulitis. The group 2 rats had (a) normal glycaemic response to oral and intraperitoneal glucose, tolbutamide and arginine on further testing; (b) normal fasting insulin but excessive insulin response to glucose and tolbutamide, but not to arginine, and (c) mainly normal islet morphology. Thus, impaired glucose tolerance may occur in BB rats with either hypoinsulinaemia or hyperinsulinaemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00275949
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  • 5
    Electronic Resource
    Electronic Resource
    Blood glucose regulation using closed- and open-loop insulin delivery systems (1979)
    Springer
    Diabetologia 17 (1979), S. 45-49 
    Details
    ISSN: 1432-0428
    Keywords: Blood glucose regulation and control ; glucose infusion ; continuous low dose peripheral insulin infusion ; pancreatectomized dogs ; artificial beta cell ; hyperinsulinaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucose was infused into anaesthetized dogs before and after pancreatectomy. In the diabetics blood glucose was regulated first by closed-loop and then by open-loop insulin delivery schemes. Insulin requirements for the latter were determined by resolving the former into a sequence of 3 different infusion rates: during the baseline and recovery periods, basal insulin was delivered at 0.37±0.02 mU/kg/min, while during the 60 min glucose infusion (10 mg/kg/min) there was an 8 min infusion at 4.96±0.37 mU/kg/min and a 52 min component at 1.85±0.08 mU/kg/min. With the open-loop method under these highly standardized conditions glycaemia was similar to normal controls but IRI levels were significantly higher, 13.5 vs 8.0 μU/ml (p〈0.05) in the baseline and recovery periods and 74 vs 25 μU/ml (p〈0.05) during the glucose infusion. It was concluded that: constant normogly-caemia can be maintained in the basal state by a constant rate of peripheral insulin delivery but at rates resulting in peripheral hyperinsulinaemia; the glycaemic response to glucose infusion can be normalized by a two component waveform of insulin delivery; and the closed-loop method can serve as a useful guide in determining insulin requirements.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01222977
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  • 6
    Electronic Resource
    Electronic Resource
    The spontaneously diabetic Wistar rat (the “BB” rat) (1978)
    Springer
    Diabetologia 14 (1978), S. 199-207 
    Details
    ISSN: 1432-0428
    Keywords: Animal model ; spontaneous diabetes ; juvenile diabetes ; plasma glucose ; insulin ; glucagon ; ketones ; oral glucose tolerance tests ; chemical diabetes ; insulitis ; free fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A longitudinal study of 51 weanlings from 5 litters of “BB” Wistar rats was undertaken to characterize the time course of the spontaneous diabetic syndrome. Nine rats developed overt diabetes. An abnormal glucose tolerance preceded the onset of the syndrome in 6 of these 9 rats. No other “clinical” or metabolic variable measured was predictive of the development of this syndrome. In these rats, the onset was remarkably abrupt, followed by rapid clinical deterioration with marked hyperglycaemia, glycosuria, ketonaemia and hypoinsulinaemia attained within 2 to 8 days. Pronounced insulitis was present in the early stages of the syndrome, resulting in complete B-cell destruction at the time of sacrifice at 7 to 40 days. Among the 42 littermates, 9 revealed sequential abnormalities in oral glucose tolerance tests performed at weekly intervals (to age 90–120 d) though remaining aglycosuric and maintaining normal fasting plasma glucose levels. In 7 of these rats, a milder form of the same islet inflammatory lesion seen in the overtly diabetic animals was present. Thus the new features identified are: 1) a time course of evolution from normoglycaemia to overt diabetes telescoped into a period of days, and 2) a “chemical” stage or form with an insulitis similar to that found in the early stages of overt diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00429781
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  • 7
    Electronic Resource
    Electronic Resource
    Seventh Annual Meeting of the European Association for the Study of Diabetes (1972)
    Springer
    Diabetologia 8 (1972), S. 53-72 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01219987
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  • 8
    Electronic Resource
    Electronic Resource
    The diabetic syndrome of the ‘BB’ Wistar rat: Possible relevance to Type 1 (insulin-dependent) diabetes in man (1982)
    Springer
    Diabetologia 22 (1982), S. 225-232 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes ; animal ‘model’ ; lymphopenia ; immunity ; insulin ; glucagon ; neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The diabetes which occurs spontaneously in the ‘BB’ Wistar rat has many affinities with human Type 1 (insulin-dependent) diabetes. It occurs in a non-obese, standard, laboratory rat derived from a non-inbred Wistar line. Both sexes are affected, with onset corresponding approximately to the time of sexual maturation. Both genetic and immune factors are involved in the aetiology, but their precise nature remains to be defined. Evolution of the overt clinical syndrome occurs over a period of hours to a few days. An intense insulitis is found, accompanied by selective destruction of B cells. Although insulitis may precede diabetes by many weeks, within 7–21 days after glycosuria the B cells are completely destroyed and have disappeared and the islets are few, small and with little residual inflammation. If untreated, marked wasting of body tissues, including fat and muscle protein, dehydration, and ketosis supervene. Careful study of littermates reveals glucose intolerance in 10%–25%, accompanied always by insulitis and these rats may subsequently develop insulin-dependent diabetes. Marked lymphopenia, mainly of thymus-derived (T) lymphocytes, both precedes and is sustained during glucose intolerance and overt diabetes. This lymphopenia appears to be associated reliably with insulitis, and may be a simple marker of susceptibility thereto. Abnormalities of nerves, testicles, and a tendency towards increased frequency of lymphomas have been found. Further research in this animal could lead to insights into aetiology, pathophysiology and complications potentially applicable to man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00281296
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  • 9
    Electronic Resource
    Electronic Resource
    Exercise and diabetes (1981)
    Springer
    Diabetologia 21 (1981), S. 237-237 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00252661
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  • 10
    Electronic Resource
    Electronic Resource
    Islet cell surface and lymphocyte antibodies often precede the spontaneous diabetes in the BB rat (1984)
    Springer
    Diabetologia 26 (1984), S. 159-165 
    Details
    ISSN: 1432-0428
    Keywords: BB rats ; islet cell surface antibodies ; lymphocyte antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The diabetic syndrome of the BB rat shows many homologies with that of human insulin-dependent diabetes and evidence that the onset of the disease is associated with the presence of autoantibodies, including islet cell surface antibodies. In this study, sera were sampled serially from weaning to 157 days of age from 26 BB rats in two low-incidence litters, and 22 rats of three high-incidence litters. Clinical and metabolic variables were monitored concurrently with blood lymphocyte counts. Islet morphology was correlated at sacrifice. In the high-incidence litters, eight rats developed insulin-dependent diabetes, five impaired glucose tolerance, and the remaining nine all showed insulitis. In the low-incidence litters, only one animal showed impaired glucose tolerance and another insulitis. In the high-incidence litters 16 rats (73%) had islet cell surface antibodies compared with 4 out of 26 (15%) low-incidence controls (p〈0.002). Antibodies reactive with Wistar rat spleen lymphocytes were present in all high-incidence rats compared with 19% (5 out of 26) among the control litters (p〈0.002). Time courses of islet cell surface and lymphocyte antibody appearance and their peak values varied, but already at weaning the levels of both antibodies were increased among the high-incidence litter rats (p〈 0.001). Islet cell surface and/or lymphocyte antibodies were therefore present in the majority of animals at an age where neither morphological nor metabolic evidence of the diabetic syndrome were yet detected. All rats that showed any form of the syndrome were lymphopenic. These findings suggest that BB rats have an abnormal immune response which predisposes to later development of insulin-dependent diabetes, often preceded by the presence of islet cell surface and/or lymphocyte antibodies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00281126
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