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  • 1
    Electronic Resource
    Electronic Resource
    Relative contribution of glycogenolysis and gluconeogenesis to hepatic glucose production in control and diabetic rats. A re-examination in the presence of euglycaemia (1998)
    Springer
    Diabetologia 41 (1998), S. 307-314 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Hepatic glucose production ; gluconeogenesis ; glycogenolysis ; insulin resistance ; fasting hyperglycaemia ; glucose clamp.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several studies have suggested that, in non-insulin-dependent diabetes mellitus, augmented gluconeogenesis is responsible for increased endogenous glucose production (EGP) and in the end determines fasting hyperglycaemia. However, human and animal studies have been conducted by comparing euglycaemic control subjects to hyperglycaemic diabetic probands. We measured EGP and hepatic gluconeogenesis comparing control and diabetic rats in the fasting state (with diabetic animals in hyperglycaemia), re-examining them in the presence of identical euglycaemia (with diabetic rats made acutely euglycaemic through i. v. phloridzin) or during a hyperinsulinaemic clamp. All rats were infused with [3-3H]-glucose and [U-14C]-lactate; the ratio between 14C-uridine-diphosphoglucose (reflecting 14C-glucose 6-phosphate) and 2 ·14C-phosphoenolpyruvate specific activities (both purified by high performance liquid chromatography from liver) measured hepatic gluconeogenesis. In diabetic animals, although overall EGP ( ∼ 19.5 mg · kg–1· min–1) remained unaffected by experimental euglycaemia, the contribution of glycogenolysis largely increased (from 5.4 to 11.7 mg · kg–1· min–1, hyper- vs euglycaemia) while gluconeogenesis decreased (from 14.0 to 8.1 mg · kg–1æ min–1); both were responsible for the augmented EGP (control rats, EGP: 12.7 mg · kg–1· min–1; gluconeogenesis: 5.9 mg · kg–1· min–1; glycogenolysis: 6.7 mg · kg–1· min–1). Finally, during insulin clamp, gluconeogenesis and glycogenolysis were similarly decreased, and both contributed to the hepatic insulin-resistance of diabetic animals. We conclude that, in this model of non-insulin-dependent diabetes, augmented gluconeogenesis is not primarily responsible for fasting hyperglycaemia and hepatic insulin resistance. Finally, failure to accurately match the experimental conditions in which diabetic and control humans or animals are compared affects gluconeogenesis, overestimating its role in determining hyperglycaemia. [Diabetologia (1998) 41: 307–314]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050908
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  • 2
    Electronic Resource
    Electronic Resource
    In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: Possible relevance to the maladaptive responses to chronic hyperglycaemia (1995)
    Springer
    Diabetologia 38 (1995), S. 518-524 
    Details
    ISSN: 1432-0428
    Keywords: Key words Glucosamine ; insulin resistance ; insulin secretion ; glucose toxicity ; glucose clamp.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We tested the hypothesis that glucosamine, a putative activator of glucose toxicity in vitro through acceleration of the hexosamine pathway, may determine in vivo the two key features of glucose toxicity in diabetes, namely, peripheral insulin resistance and decreased insulin secretion. Two groups of awake rats were studied either with intra-arterial administration of glucosamine (5 μmol · kg–1· min–1) or saline. Insulin secretion was determined after arginine, glucose (hyperglycaemic clamp), and arginine/glucose infusions, while insulin-mediated glucose metabolism was assessed by the euglycaemic hyperinsulinaemic clamp in combination with [3–3H]-glucose infusion. Glucosamine had no effects on arginine-induced insulin secretion both at euglycaemia and hyperglycaemia, but significantly (40–50 %) impaired glucose-induced insulin secretion (both first and second phases). During euglycaemic hyperinsulinaemic clamp studies, glucosamine decreased glucose uptake by ∼ 30 %, affecting glycolysis (estimated from 3H2O rate of appearance) and muscle glycogen synthesis (calculated from accumulation of [3H]–glucosyl units in muscle glycogen) to a similar extent. Muscle glucose 6–phosphate concentration was markedly reduced in the glucosamine–infused rats, suggesting an impairment in glucose transport/phosphorylation. Therefore, an increase in hexosamine metabolism in vivo: 1) inhibits glucose–induced insulin secretion, and 2) reduces insulin stimulation of both glycolysis and glycogen synthesis, thereby mimicking in normal rats the major alterations due to glucose toxicity in diabetes. [Diabetologia (1995) 38: 518–524]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400719
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  • 3
    Electronic Resource
    Electronic Resource
    In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: Possible relevance to the maladaptive responses to chronic hyperglycaemia (1995)
    Springer
    Diabetologia 38 (1995), S. 518-524 
    Details
    ISSN: 1432-0428
    Keywords: Glucosamine ; insulin resistance ; insulin secretion ; glucose toxicity ; glucose clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We tested the hypothesis that glucosamine, a putative activator of glucose toxicity in vitro through acceleration of the hexosamine pathway, may determine in vivo the two key features of glucose toxicity in diabetes, namely, peripheral insulin resistance and decreased insulin secretion. Two groups of awake rats were studied either with intraarterial administration of glucosamine (5 Μmol·kg−1· min−1) or saline. Insulin secretion was determined after arginine, glucose (hyperglycaemic clamp), and arginine/glucose infusions, while insulin-mediated glucose metabolism was assessed by the euglycaemic hyperinsulinaemic clamp in combination with [3-3H]-glucose infusion. Glucosamine had no effects on arginine-induced insulin secretion both at euglycaemia and hyperglycaemia, but significantly (40–50%) impaired glucose-induced insulin secretion (both first and second phases). During euglycaemic hyperinsulinaemic clamp studies, glucosamine decreased glucose uptake by ∼30%, affecting glycolysis (estimated from 3H2O rate of appearance) and muscle glycogen synthesis (calculated from accumulation of [3H]-glucosyl units in muscle glycogen) to a similar extent. Muscle glucose 6-phosphate concentration was markedly reduced in the glucosamine-infused rats, suggesting an impairment in glucose transport/phosphorylation. Therefore, an increase in hexosamine metabolism in vivo: 1) inhibits glucose-induced insulin secretion, and 2) reduces insulin stimulation of both glycolysis and glycogen synthesis, thereby mimicking in normal rats the major alterations due to glucose toxicity in diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400719
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Chronic primary hyperinsulinaemia is associated with altered insulin receptor mRNA splicing in muscle of patients with insulinoma (1996)
    Springer
    Diabetologia 39 (1996), S. 220-225 
    Details
    ISSN: 1432-0428
    Keywords: Insulin receptor ; alternative splicing ; hyperinsulinism ; insulin resistance ; insulinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alternative splicing of the 36-base pair exon 11 of the human insulin receptor gene results in the synthesis of two insulin receptor isoforms with distinct functional characteristics (the isoform containing exon 11 has lower insulin binding affinity and lower internalization rate). Altered expression of these insulin receptor isoforms has been previously demonstrated in skeletal muscle of patients with non-insulin-dependent diabetes mellitus (NIDDM). However, this observation was not confirmed by other studies and is still a matter of controversy; furthermore, it is not known whether it represents a primary event or is secondary to hyperinsulinaemia and insulin resistance. In order to address this issue in patients with pure non-genetically determined hyperinsulinaemia, we examined the alternative splicing of insulin receptor mRNAs in skeletal muscle of eight patients with surgically confirmed insulinoma and insulin resistance and in eight healthy subjects, using the reverse transcriptase-polymerase chain reaction technique. The insulinoma patients displayed a significant increase in the expression of the insulin receptor isoform containing exon 11 (75.7±2.3%) when compared with normal subjects (57.9±1.5%); furthermore, this increase was positively correlated with plasma insulin concentration and negatively correlated with in vivo insulin sensitivity (glucose clamp). In conclusion, the increased expression of the insulin receptor isoform with lower insulin binding affinity in patients with primary non-genetically determined hyperinsulinaemia supports a role for insulin in the regulation of alternative splicing of insulin receptor pre-mRNA and suggests that in NIDDM an altered receptor isoform distribution might be secondary to the ambient hyperinsulinaemia rather than representing a primary defect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403966
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  • 5
    Electronic Resource
    Electronic Resource
    Increased adipose tissue PC-1 protein content, but not tumour necrosis factor-a gene expression, is associated with a reduction of both whole body insulin sensitivity and insulin receptor tyrosine-kinase activity (1997)
    Springer
    Diabetologia 40 (1997), S. 282-289 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Adipose tissue ; insulin sensitivity ; insulin tolerance test ; insulin receptor tyrosine-kinase inhibitors ; tumour necrosis factor-α ; PC-1.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study we measured PC-1 content, tumour necrosis factor (TNF)-α gene expression, and insulin stimulation of insulin receptor tyrosine-kinase activity in adipose tissue from non-obese, non-diabetic subjects. These parameters were correlated with in vivo insulin action as measured by the intravenous insulin tolerance test (Kitt values). PC-1 content was negatively correlated with Kitt values (r = –0.5, p = 0.04) and positively with plasma insulin levels both fasting (r = 0.58, p = 0.009) and after 120 min during oral glucose tolerance test (OGTT) (r = 0.67, p = 0.002). Moreover, adipose tissue PC-1 content was higher in relatively insulin-resistant subjects (Kitt values lower than 6) than in relatively insulin-sensitive subjects (Kitt values higher than 6) (525 ± 49 ng/mg protein vs 336 ± 45, respectively, p = 0.012). Adipose tissue insulin receptor tyrosine-kinase activity in response to insulin was significantly lower at all insulin concentrations tested (p = 0.017, by two-way analysis of variance test) in insulin-resistant than in insulin-sensitive subjects (Kitt values lower or higher than 6, respectively). In contrast to PC-1, no significant correlation was observed between adipose tissue TNF-α mRNA content and Kitt values, and plasma insulin levels, both fasting and at after 120 min during OGTT. Also, no difference was observed in TNF-α mRNA content between subjects with Kitt values higher or lower than 6. These studies in adipose tissue, together with our previous studies in skeletal muscle raise the possibility that PC-1, by regulating insulin receptor function, may play a role in the degree of insulin sensitivity in non-obese, non-diabetic subjects. [Diabetologia (1997) 40: 282–289]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050675
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  • 6
    Electronic Resource
    Electronic Resource
    Serum triglyceride levels in uremic patients receiving polyacrylonitrile dialysis
    Amsterdam : Elsevier
    Clinical Biochemistry 14 (1981), S. 72-73 
    Details
    ISSN: 0009-9120
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0009-9120(81)90721-9
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    Paper (German National Licenses)
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  • 7
    Electronic Resource
    Electronic Resource
    High density lipoprotein cholesterol distribution and predictive power in some Italian populations studies (1989)
    Springer
    European journal of epidemiology 5 (1989), S. 328-335 
    Details
    ISSN: 1573-7284
    Keywords: HDL-cholesterol ; Cardiovascular risk factors ; Prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nine Italian population samples, for a total of 12,365 males and 8,043 females aged 11 to 84, were examined. The age and sex distribution of HDL-cholesterol levels were calculated for studying its relationship with major cardiovascular risk factors, and for estimating its predictive power on coronary events and on all causes of mortality. Mean values of HDL-cholesterol in the pool of the samples ranged, according to different age groups, from 46.4 to 56.8 mg/dl in males and from 53.7 to 55.8 mg/dl in females. The linear correlation coefficients between HDL-cholesterol and 10 risk factors did not show high levels except those with triglycerides in men aged 20-34 (−0.33) and 35–64 (−0.34). Using the multiple linear regression model the levels of HDL-cholesterol were estimated as a function of the 10 risk factors solving 4 equations (for males, females and for two age groups, 20–34 and 35–64). The factors showing significant coefficients were body mass index (negative), triglycerides (negative), cigarette smoking (negative), alcohol consumption (positive), physical activity (positive), and non-HDL-cholesterol (negative). The Cox model was used for the prediction of coronary death and all causes of death and the logistic function for the prediction of coronary incidence in two of the studies on men aged 46–65 (6 year follow-up) and aged 60–79 (5 year follow-up), and including 5 other factors as possible confounders. Only the univariate prediction of coronary deaths in one study (men aged 46–65) provided a significant coefficient for HDL-cholesterol (t = −2.7624).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00144833
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  • 8
    Electronic Resource
    Electronic Resource
    The prediction of future health in healthy middle-aged men (1986)
    Springer
    European journal of epidemiology 2 (1986), S. 233-239 
    Details
    ISSN: 1573-7284
    Keywords: Risk factors ; Health prediction ; Multivariate analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two cohorts of men aged 49–59 at entry, representing cluster samples of two rural areas in Northern and Central Italy, for a total of 1712 subjects have been followed-up for 20 years within an epidemiological study originally designed for cardiovascular disease. After 20 years, only 41 men have been judged to have remained substancially healthy throughout the observation period, i.e. free from a number of major diseases. Univariate and multivariate analyses trying to predict the maintenance of health status showed that among 21 selected characteristics only the following one had a significant power: age, cigarette smoking (adverse effect) and vital capacity( favourable effect). A minor role was also played by the body mass index (adverse effect) and forced expiratory volume (favourable effect). Those who did not remain healthy exibited a greater increase in blood pressure and body mass index.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00211537
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