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  • 1
    Electronic Resource
    Electronic Resource
    The course and determinants of insulin action in Type 1 (insulin-dependent) diabetes mellitus (1989)
    Springer
    Diabetologia 32 (1989), S. 20-27 
    Details
    ISSN: 1432-0428
    Keywords: Insulin resistance ; time-course ; euglycaemic clamp ; Type 1 (insulin-dependent) diabetes ; insulin action ; glycaemic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The course and determinants of insulin action were investigated in 8 newly diagnosed Type 1 (insulin-dependent) diabetic patients, who were studied every 3 months for one year, and in three groups of 8 patients each with 5, 10 and 20 years diabetes, studied once. Fifteen healthy subjects matched for age, sex and body weight served as control subjects. Dose-response curves were constructed using sequential euglycaemic (5.0 mmol/l) clamps (insulin infusion rates: 0.5, 1.0, 2.0 and 5.0 mU·kg−1·min−1 in periods of 2h). After 1/2 month of insulin treatment, insulin responsiveness was normal, but sensitivity was decreased (ED50 70±7 mU/l (SEM) vs 54±4mU/l in control subjects, p〈0.05). After 6 months, insulin sensitivity was improved (ED50 57±4 mU/l, p〈0.01 vs 1/2 month and not significant (NS) vs control subjects); but after 9 and 12 months, it was reduced again, similarly to 0.5 month. Insulin responsiveness remained normal at all time-points. In the three groups of patients with longstanding diabetes, impaired insulin sensitivity with normal responsiveness was noted also (ED50 73±9 mU/l, p〈0.02 vs control subjects). At 6, 9 and 12 months, glycaemic control (HbA1) and insulin dose were inverse correlates for insulin action; in patients with longstanding disease, this was noted for HbA1 and body weight, in control subjects for body weight. In conclusion, decreased insulin sensitivity re-develops in Type 1 diabetes within the first year following an initial improvement. Presumably, hyperglycaemia plays a role in the pathogenesis of this recurrence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265399
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  • 2
    Electronic Resource
    Electronic Resource
    Amylin-induced in vivo insulin resistance in conscious rats: the liver is more sensitive to amylin than peripheral tissues (1991)
    Springer
    Diabetologia 34 (1991), S. 218-224 
    Details
    ISSN: 1432-0428
    Keywords: Amylin ; islet amyloid polypeptide ; glucose production ; glucose uptake ; in vivo ; clamp ; counterregulatory hormones ; insulin action ; insulin receptor ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Amylin is a polypeptide of 37 amino acids, predominantly synthesized in pancreatic Beta cells. The peptide was suggested to be dysregulated in Type 2 (non-insulin-dependent) diabetes mellitus and it antagonized certain actions of insulin in vitro in rat muscle. This led to speculation that amylin is involved in the pathogenesis of Type 2 diabetes. We have examined the in vivo effects of rat amylin, amidated at the carboxy-terminus, on insulin-mediated carbohydrate metabolism in conscious rats, using the hyperinsulinaemic (±1 nmol/l) euglycaemic (6 mmol/l) clamp technique combined with [3-3H]-glucose infusion. Basal plasma amylin levels were ≤75 pmol/l. Applied amylin levels of 220±75 pmol/l (infusion rate of 12.5 pmol/min) antagonized only the insulin action on liver, resulting in a 100% increase of hepatic glucose output. Amylin levels of 4750±750 pmol/l (infusion rate of 125 pmol/min) induced a 250% increase of insulin-inhibited hepatic glucose output and, in addition, a 30% decrease of insulin-stimulated peripheral glucose uptake. Amylin did not affect: 1) the metabolic clearance rate of insulin, 2) the levels of plasma glucagon, epinephrine, norepinephrine, and corticosterone, 3) in vitro insulin binding and insulin-stimulated receptor autophosphorylation. This suggests that amylin antagonizes insulin action via binding to a yet unknown receptor. In conclusion: amylin causes in vivo insulin resistance and the liver seems the predominant organ regulated by this hormone. The in vivo effects of amylin mimic the pathophysiological abnormalities of insulin action in Type 2 diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00405079
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  • 3
    Electronic Resource
    Electronic Resource
    Impact of donor-related variables on islet isolation outcome in dogs (1994)
    Springer
    Diabetologia 37 (1994), S. 111-114 
    Details
    ISSN: 1432-0428
    Keywords: Morphometry ; donor ; islet ; isolation ; pancreas ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical human islet transplantation programmes are considerably hampered by the variability of islet isolation outcome. The effects of the islet content of the pancreas and other donor-related variables on isolation outcome have not been evaluated systematically so far — either in large animals, or in man. We studied the impact of interindividual differences in age, body weight and pancreatic islet content on the outcome of collagenase isolation of islets from the splenic pancreas of beagle dogs (n=31). The islet volume of the splenic pancreas amounted to a mean (± SEM) 15.7±0.9 μl per gramme pancreas, and varied three-fold (from 8.4 to 27.3 μl). Isolated islet yield was 7.6±0.7 μl/g and varied nine-fold (1.8–16.3 μl). Animals also varied in age eight-fold (867 months) and body weight two-fold (8.6–18.3 kg). Differences in body weight and age explained 60% of variance in the fractional islet volume of the pancreas and 50% of the variance in islet yield (p〈0.001). Fractional islet volume of the splenic pancreas also explained 50% of the variance in islet yield (p〈0.001). We conclude that the outcome of islet isolation may be predictable after controlling for the variable islet content of pancreases, and other donor-related variables, and suggest that similar studies should be done in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428786
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  • 4
    Electronic Resource
    Electronic Resource
    Impact of donor-related variables on islet isolation outcome in dogs (1994)
    Springer
    Diabetologia 37 (1994), S. 111-114 
    Details
    ISSN: 1432-0428
    Keywords: Key words Morphometry, donor, islet, isolation, pancreas, dog.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical human islet transplantation programmes are considerably hampered by the variability of islet isolation outcome. The effects of the islet content of the pancreas and other donor-related variables on isolation outcome have not been evaluated systematically so far – either in large animals, or in man. We studied the impact of interindividual differences in age, body weight and pancreatic islet content on the outcome of collagenase isolation of islets from the splenic pancreas of beagle dogs (n =31). The islet volume of the splenic pancreas amounted to a mean (± SEM) 15.7±0.9 µl per gramme pancreas, and varied three-fold (from 8.4 to 27.3 µl). Isolated islet yield was 7.6±0.7 µl/g and varied nine-fold (1.8–16.3 µl). Animals also varied in age eight-fold (8–67 months) and body weight two-fold (8.6–18.3 kg). Differences in body weight and age explained 60 % of variance in the fractional islet volume of the pancreas and 50 % of the variance in islet yield (p〈0.001). Fractional islet volume of the splenic pancreas also explained 50 % of the variance in islet yield (p〈0.001). We conclude that the outcome of islet isolation may be predictable after controlling for the variable islet content of pancreases, and other donor-related variables, and suggest that similar studies should be done in man. [Diabetologia (1994) 37: 111–114]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428786
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  • 5
    Electronic Resource
    Electronic Resource
    Function and survival of intrasplenic islet autografts in dogs (1996)
    Springer
    Diabetologia 39 (1996), S. 37-44 
    Details
    ISSN: 1432-0428
    Keywords: Islet of Langerhans ; transplantation ; metabolism ; dog ; glucose-dependent insulinotropic polypeptide ; pancreatic polypeptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Successful transplantation of isolated islets of Langerhans has been reported in large mammals, including man, but metabolic control has not been well-established. We studied the glucose and islet hormone response to fasting, i. v. glucose bolus infusion, i.v. arginine bolus infusion during a 35-mmol/l hyperglycaemic clamp, mixed meals, and i. v. insulin-induced hypoglycaemia up to 3 years after intrasplenic islet autotransplantation in six pancreatectomised dogs. The individual postprandial insulinogenic index (ratio of 2-h postprandial insulin to glucose levels) at 1 month post-transplant, predicted (r=0.99) the time to functional graft failure (6–175 weeks). Metabolic studies at 6 months post-transplant in four dogs demonstrated normal fasting glucose and hormone levels, except for reduced pancreatic polypeptide levels. Intravenous glucose and arginine-stimulated insulin were reduced to 15% of preoperative values. In contrast, postprandial normoin-sulinaemia was observed — albeit with moderate hyperglycaemia (approximately 10 mmol/l). Postprandial glucagon and glucose-dependent insulinotropic polypeptide (GIP) had increased. Comparison of the post-transplant insulin responses to a meal and to intravenous challenges demonstrated maximal stimulation of the graft by the meal. Post-transplant pancreatic polypeptide responses to a meal and i.v. arginine were severely reduced, and no pancreatic polypeptide response to i.v. insulin-induced hypoglycaemia was observed — indicating absence of cholinergic reinnervation. Thus, glucose regulation and both the insulin secretory capacity and life expectancy of islet grafts were best documented by meal testing. Tentatively, a postprandial hyperglycaemia-enhanced incretin effect of glucose-dependent insulinotropic polypeptide and other gut hormones may account for the difference in the insulin response to i. v. glucose and a meal. Aside from the reduced insulin secretory capacity, both a deranged pulsatile delivery of insulin, hyperglucagonaemia, and pancreatic polypeptide deficiency may have been conducive to glucose intolerance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400411
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  • 6
    Electronic Resource
    Electronic Resource
    Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM (1997)
    Springer
    Diabetologia 40 (1997), S. 843-849 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Oestrogen therapy ; non-insulin-dependent diabetes mellitus ; glucose regulation ; insulin sensitivity ; hepatic glucose production ; lipoprotein profiles ; coagulation factors ; fibrinolysis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin-dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for patients with NIDDM. In a double blind randomized placebo controlled trial we assessed the effect of oral 17 β -estradiol during 6 weeks in 40 postmenopausal women with NIDDM. Glycated haemoglobin (HbA1c), insulin sensitivity, suppressibility of hepatic glucose production, lipoprotein profile and parameters of fibrinolysis were determined. The oestrogen treated group demonstrated a significant decrease of HbA1c and in the normotriglyceridaemic group a significantly increased suppression of hepatic glucose production by insulin. Whole body glucose uptake and concentrations of non-esterified fatty acids did not change. LDL-cholesterol- and apolipoprotein B levels decreased, and HDL-cholesterol, its subfraction HDL2-cholesterol and apolipotrotein A1 increased. The plasma triglyceride level remained similar in both groups. Both the concentration of plasminogen activator inhibitor-1 antigen and its active subfraction decreased. Tissue type plasminogen activator activity increased significantly only in the normotriglyceridaemic group. Oestrogen replacement therapy improves insulin sensitivity in liver, glycaemic control, lipoprotein profile and fibrinolysis in postmenopausal women with NIDDM. For a definite answer as to whether oestrogens can be more liberally used in NIDDM patients, long term studies including the effect of progestogens are necessary. [Diabetologia (1997) 40: 843–849]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050758
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  • 7
    Electronic Resource
    Electronic Resource
    The relative contribution of insulin secretory capacity, insulin action, and incretins to metabolic control after islet transplantation in dogs (1999)
    Springer
    Journal of molecular medicine 77 (1999), S. 104-106 
    Details
    ISSN: 1432-1440
    Keywords: Key words Islet of Langerhans ; Transplantation ; Function ; Incretin ; GLP-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adequate metabolic control is central to the concept of islet transplantation, but has received limited attention. We studied metabolic control in 8 dogs at 6–9 months after intrasplenic autografting of ∼25% of the normal mass islets – as compared to 30 controls. A similar posttransplant reduction to ∼25% of the insulin secretory capacity as assessed by intravenous arginine stimulation during 35 mM glucose clamps, mirrored the reduction of the islet mass. Postprandially, in contrast, the insulin response had increased to 140% in the islet recipients – with a concomitant rise of glycemia to ∼8.5 mM. Posttransplant, the insulin secretory capacity correlated both with the index of insulin action (which averaged 55% of the normal value) as assessed by euglycemic hyperinsulinemic clamps, and – inverse – with the postprandial glucose excursions. Because insulin action did not correlate with postprandial glucose, the insulin secretory capacity appears to be the primary determinant of the impaired glucose tolerance. Marked postprandial hyperglucagonemia, and a virtually absent pancreatic polypeptide response in the grafted animals, may also have contributed to the impaired glucose tolerance. Posttransplant, infusion of a physiological dose of the gut hormone glucagon-like peptide-1 during 8.5 mM glucose clamps – mimicking the postprandial glycemia – potentiated glucose-stimulated insulin 175%. Thus, after transplantation of a suboptimal islet mass, postprandial glucose excursions are restrained by hyperglycemic potentiation of the entero-insular axis, which may account for the difference in the insulin response to the intravenous and oral challenges. Because, the insulin secretory capacity reflects the islet mass and appears to be the major determinant of glucoregulation, transplantation of a larger islet mass may allow near-normal glycemic control.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050312
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  • 8
    Electronic Resource
    Electronic Resource
    Cerebral vasoconstriction in comatose patients resuscitated from a cardiac arrest? (1996)
    Springer
    Intensive care medicine 22 (1996), S. 1191-1196 
    Details
    ISSN: 1432-1238
    Keywords: Cardiac arrest ; Delayed hypoperfusion phase ; Cerebral oxygen extraction ; Endothelin ; Nitrate ; cGMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To determine the role of cerebral vasoconstriction in the delayed hypoperfusion phase in comatose patients after cardiac arrest. Design Prospective study. Setting Medical intensive care unit in a university hospital. Patients 10 comatose patients (Glasgow Coma Score ≤6) successfully resuscitated from a cardiac arrest occurring outside the hospital. Measurements We measured the pulsatility index (PI) and mean blood flow velocity (MFV) of the middle cerebral artery, the cerebral oxygen extraction ratio and jugular bulb levels of endothelin, nitrate, and cGMP during the first 24 h after cardiac arrest. Results The PI decreased significantly from 1.86±1.02 to 1.05±0.22 (p=0.03). The MFV increased significantly from 29±10 to 62±25 cm/s (p=0.003). Cerebral oxygen extraction ratio decreased also from 0.39±0.13 to 0.24±0.11 (p=0.015). Endothelin levels were high but did not change during the study period. Nitrate levels varied widely and showed a slight but significant decrease from 37.1 μmol/l (median; 25th–75th percentiles: 26.8–61.6) to 31.3 μmol/l (22.1–39.6) (p=0.04). Cyclic guanosine monophosphate levels increased significantly from 2.95 nmol/l (median; 25th–75th percentiles: 2.48–5.43) to 7.5 nmol/l (6.2–14.0) (p=0.02). Conclusions We found evidence of increased cerebrovascular resistance during the first 24 h after cardiac arrest with persistent high endothelin levels, gradually decreasing nitrate levels, and gradually increasing cGMP levels. This suggests that active cerebral vasoconstriction due to an imbalance between local vasodilators and vasoconstrictors plays a role in the delayed hypoperfusion phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01709335
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  • 9
    Electronic Resource
    Electronic Resource
    Predictive value of tetrapolar body impedance measurements for hydration status in critically ill patients (1995)
    Springer
    Intensive care medicine 21 (1995), S. 125-131 
    Details
    ISSN: 1432-1238
    Keywords: Body weight ; Water and electrolyte balance ; Water loss ; Insensible ; Bioelectrical impedance ; Electric conductivity ; Critical care ; Human ; Adult
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To design and evaluate a simple and rapid method to predict body hydration status in critically ill patients. Design Prospective, consecutive sample. Setting Medical intensive care unit of a university hospital. Patients 31 consecutive patients. Methods All patients were classified daily for hydration status by the attending physician based on clinical impression, weight changes and laboratory measurements. The hydration status was scored as ‘dehydrated’, ‘euvolemic’ or ‘edematous’. The total body impedance was measured daily by a tetrapolar impedance technique. Results Resistances 〉700Ω were found in dehydrated subjects and resistances of 〈400 Ω in edematous patients. Weight gain was observed in dehydrated and weight loss in edematous patients. A discriminant analysis was used to create a predictive model for hydration using the daily impedance and weight measurements. If a cutoff point of 60% for the predicted classification was used to categorize the patient's hydration as dehydrated, euvolemic and edematous, no false positive predictions were observed for the dehydrated or the edematous state. Conclusion Impedance measurements are in close agreement with the clinical impression of hydration of critically ill patients. Future investigations must elucidate the clinical importance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01726535
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  • 10
    Electronic Resource
    Electronic Resource
    Cerebral vasoconstriction in comatose patients resuscitated from a cardiac arrest? (1996)
    Springer
    Intensive care medicine 22 (1996), S. 1191-1196 
    Details
    ISSN: 1432-1238
    Keywords: Key words Cardiac arrest ; Delayed hypoperfusion phase ; Cerebral oxygen extraction ; Endothelin ; Nitrate ; cGMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine the role of cerebral vasoconstriction in the delayed hypoperfusion phase in comatose patients after cardiac arrest. Design: Prospective study. Setting: Medical intensive care unit in a university hospital. Patients: 10 comatose patients (Glasgow Coma Score ≤6) successfully resuscitated from a cardiac arrest occurring outside the hospital. Measurements: We measured the pulsatility index (PI) and mean blood flow velocity (MFV) of the middle cerebral artery, the cerebral oxygen extraction ratio and jugular bulb levels of endothelin, nitrate, and cGMP during the first 24 h after cardiac arrest. Results: The PI decreased significantly from 1.86±1.02 to 1.05±0.22 (p=0.03). The MFV increased significantly from 29±10 to 62±25 cm/s (p=0.003). Cerebral oxygen extraction ratio decreased also from 0.39±0.13 to 0.24±0.11 (p=0.015). Endothelin levels were high but did not change during the study period. Nitrate levels varied widely and showed a slight but significant decrease from 37.1 μmol/l (median; 25th–75th percentiles: 26.8–61.6) to 31.3 μmol/l (22.1–39.6) (p=0.04). Cyclic guanosine monophosphate levels increased significantly from 2.95 nmol/l (median; 25th–75th percentiles: 2.48–5.43) to 7.5 nmol/l (6.2–14.0) (p=0.02). Conclusions: We found evidence of increased cerebrovascular resistance during the first 24 h after cardiac arrest with persistent high endothelin levels, gradually decreasing nitrate levels, and gradually increasing cGMP levels. This suggests that active cerebral vasoconstriction due to an imbalance between local vasodilators and vasoconstrictors plays a role in the delayed hypoperfusion phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01709335
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