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  • 1
    Electronic Resource
    Electronic Resource
    Human adipose tissue in culture V. Studies on the metabolic effects of insulin (1976)
    Springer
    Diabetologia 12 (1976), S. 137-143 
    Details
    ISSN: 1432-0428
    Keywords: Adipose tissue ; insulin ; catecholamines ; glycolytic enzymes ; glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Specimens of human adipose tissue were cultured for one week with or without the addition of insulin. The basal as well as the noradrenaline-stimulated lipolysis were enhanced in the explants cultured with insulin, showing that the long-term effect of the hormone is lipolytic. However, an acute antilipolytic effect of insulin could be demonstrated in these explants in the subsequent short-term incubations. The basal rate of glucose incorporation into the lipids was enhanced in the explants cultured with insulin. When insulin was added in the short-term incubations these explants did not further respond to the hormone while this was the case with the explants cultured without insulin. Thus, it seems that prolonged exposure to insulin leads to a diminished acute effect of the hormone on glucose metabolism. However, the same explants responded to the antilipolytic effect showing that insulin was able to bind itself to the membrane. The activities of hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) were increased in large fat cells both in freshly excised tissue and in the cultured explants. However, the activity of phosphofructokinase (PFK) did not correlate with the cell size. The presence of insulin during the culture period enhanced the activities of G6PDH, PK, and LDH, while this was not found for HK or PFK. The data thus suggest that the metabolic capacity of human fat cells is enhanced by long-term exposure to insulin. Although enzyme induction could be shown for G6PDH, PK and LDH it seems unlikely that this is of importance for the increased rates of glucose metabolism in these explants since the rate-limiting enzymes, HK and PFK, were not increased. Most probably, then, this stimulating effect of insulin is exerted on the membrane and the rate of glucose transport.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428979
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  • 2
    Electronic Resource
    Electronic Resource
    Kidney transplantation in Type 1 (insulin-dependent) diabetic patients (1991)
    Springer
    Diabetologia 34 (1991), S. 668-674 
    Details
    ISSN: 1432-0428
    Keywords: Kidney transplants ; diabetic glomerulopathy ; basement membrane thickness ; mesangial volume fraction ; interstitial fibrosis ; cyclosporine ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of diabetic glomerulopathy in kidneys transplanted to diabetic patients was estimated in transplant biopsies and evaluated in relation to suspected clinical risk factors for diabetic nephropathy. Surgical biopsies were taken at baseline and at 24–36 months post-transplantation in 16 Type 1 (insulin-dependent) diabetic patients and 8 non-diabetic control subjects with a glomerular filtration rate more than 30 ml·min− at follow-up. Immunosuppressive therapy included cyclosporine in all but one case. Stereological methods were used to assess basement membrane thickness, volume fraction of mesangium per glomerulus, and volume fraction of matrix per mesangium. The volume fraction of interstitial tissue per cortex was estimated by light microscopy. After 2 years the basement membrane thickness had increased by 55 nm (SD 58 nm) in the diabetic group. This change was significantly different from that of 2 nm (SD 37 nm) in control subjects (p=0.02). Mesangial volume fraction increased significantly by 0.04 (SD 0.03) in diabetic patients, and this change was significantly different from that of -0.01 (SD 0.04) in non-diabetic patients (p=0.009). No change was detectable in the matrix expressed as fraction of mesangial volume. An increase in interstitial volume fraction from baseline to 2 years was observed, but was significant only in the diabetic group (p=0.04). The changes in structural parameters did not correlate with mean values during follow-up of glycated haemoglobin or estimated protein intake, nor was any pattern discernible in the relationship to graft tissue types. The observed increase in basement membrane thickness corresponds to that observed in native kidneys during the first years of diabetes, whereas an increase in mesangial volume fraction — using a different protocol — was not observed in the early phase of the natural development. Absence of correlation with the various risk factors may reflect an irrelevance of these variables within the current range, or their influence may be offset by stronger mechanisms in the transplant situation, and therefore does not appear in this relatively small series.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400997
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  • 3
    Electronic Resource
    Electronic Resource
    A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro-and normoalbuminuria (1995)
    Springer
    Diabetologia 38 (1995), S. 1320-1327 
    Details
    ISSN: 1432-0428
    Keywords: Key words Diabetic nephropathy ; diabetic glomerulopathy ; arteriolar hyalinosis ; juxtaglomerular arterioles ; extracellular matrix ; microalbuminuria ; stereology.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyalinization of juxtaglomerular arterioles is prominent in advanced diabetic nephropathy and may have important functional consequences. We studied the early stages of diabetic renal disease using kidney biopsy material from insulin-dependent diabetic patients, 8 with normal albumin excretion rate ( 〈 15 μg/min) and 16 with microalbuminuria (15–200 μg/min). Ten living non-diabetic kidney donors served as a control group. Median duration of diabetes was 9.5 years (range 5–31) in patients with normoalbuminuria, and 12 years (7–22) in patients with microalbuminuria (p = 0.27). The tissue was sectioned systematically, 1-μm thick sections for light microscopy at 10-μm intervals, and thin sections for electron microscopy taken at 60-μm intervals. The arterioles were identified as afferent or efferent, and total profiles were photographed (magnification 7500 × ), providing a systematic independent sample for measurements using standard stereological methods. Patients with microalbuminuria had significantly increased arteriole parameters compared with the control group: for afferent and efferent arterioles the volume fraction of matrix/media, means and (coefficient of variation, CV), was 0.47 (0.16) vs 0.33 (0.19) (p = 0.0009), and 0.62 (0.14) vs 0.45 (0.23) (p = 0.0004) and matrix-T , expressing amount of matrix per unit arteriolar surface, 2.38 (0.38) μm vs 1.44 (0.30) μm (p = 0.004), and 1.62 (0.28) μm vs 1.03 (0.34) (p = 0.0009). Patients with normoalbuminuria showed no significant differences from the control group, and had lower values than microalbuminuric patients for all parameters except the afferent matrix-T . In the normoalbuminuric group a correlation was found between parameters for afferent arterioles and those for glomerular structure. In conclusion there is arteriolar accumulation of extracellular material in the early phase of diabetic nephropathy, concomitant with early glomerulopathy. [Diabetologia (1995) 38: 1320–1327]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401765
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  • 4
    Electronic Resource
    Electronic Resource
    Echocardiographic findings in kidney transplanted Type 1 (insulin-dependent) diabetic patients with and without a pancreas transplant (1991)
    Springer
    Diabetologia 34 (1991), S. S128 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; Pancreas transplantation ; Echocardiography ; Diastolic function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Echocardiography with Doppler recordings was carried out in 14 Type 1 (insulin-dependent) diabetic recipients of pancreas and kidney transplants and in 14 Type 1 diabetic kidney transplanted control patients, matched for age, sex, duration of diabetes, extent of other late complications, time since transplantation, dose of prednisolone, and renal function. HbA1c was 5.5±0.6 vs 8.7+1.4% (pancreas transplanted vs kidney only). Both groups had a slight increase in interventricular septum thickness. Left ventricular mass was equal. The ejection fraction as a measure of systolic function was normal and equal, 0.71±0.05 vs 0.69±0.07. Diastolic function was also equal in two out of three parameters, isovolumic relaxation time and deceleration time. The A/E ratio, however, tended to be lower in the pancreas transplanted group, 0.94±0.20 vs 1.06±0.18 (p=0.04). This indicates more frequent occurrence of impaired diastolic filling in the recipients of kidney only. Follow-up will show whether diastolic dysfunction increases and may be related to the increased cardiovascular mortality in kidney transplanted Type 1 diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00587638
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  • 5
    Electronic Resource
    Electronic Resource
    Outcome of pancreas transplantations in Göteborg, Sweden 1985–1990 (1991)
    Springer
    Diabetologia 34 (1991), S. S1 
    Details
    ISSN: 1432-0428
    Keywords: Pancreas transplantation ; Graft survival ; Patient survival-Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During 1985 to 1990, 67 segmental pancreas transplantations with bladder drainage were performed. Fifty were combined pancreas and kidney and 17 were pancreas after kidney transplants. All patients were transplanted with the same technique. The 1-year actuarial pancreas graft survival for the combined patients with quadruple immunosuppressive therapy was 83% and the patient survival, 95%. The most important complications were infections, leakage from the pancreatico cystostoma and vascular complications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00587606
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  • 6
    Electronic Resource
    Electronic Resource
    Glomerular structure and function in proteinuric Type 2 (non-insulin-dependent) diabetic patients (1993)
    Springer
    Diabetologia 36 (1993), S. 1064-1070 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; diabetic nephropathy ; diabetic glomerulopathy ; basement membrane ; mesangium ; mesangial matrix ; glomerular hypertrophy ; glomerular occlusion ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glomerular ultrastructure was examined in a series of 20 Type 2 (non-insulin-dependent) diabetic patients with proteinuria. Reference was made to data previously obtained in non-diabetic kidney donors and in Type 1 (insulindependent) diabetic patients with similar degrees of proteinuria. The Type 2 diabetic patients demonstrated the changes which characterize the diabetic glomerulopathy seen in Type 1 diabetic patients: basement membrane thickening, and increase in the mesangium and mesangial matrix expressed as fraction of the glomerular volume. Among the Type 2 diabetic patients there was more variation then among the Type 1 diabetic patients, as this group included subjects with normal parameters. The group means and coefficients of variation (=SD/mean) of the glomerulopathy parameters combined in the glomerulopathy index=basement membrane thickness/10+Vv(matrix/glom)·100 were 81 (0.30) and 92 (0.15) in the two diabetic groups, clearly different from the non-diabetic index, 42 (0.16). All Type 2 diabetic patients who also had retinopathy had a glomerulopathy index above the normal range. Similar changes in glomerular composition were seen in the two diabetic groups: with increasing glomerulopathy the volume of matrix dominated over the peripheral basement membrane, and a shift in the ratio of interfaces was seen: mesangial surface towards capillary lumen increased relative to the urinary surface, and peripheral capillary surface comprised less of the total capillary surface. Data indicated marked glomerular hypertrophy, which correlated with the mesangial volume fraction, thus encompassing preserved filtration surface per glomerulus. An inverse correlation obtained between the index of glomerulopathy and current glomerular filtration rate, as well as the ensuing rate of decline in glomerular filtration rate, as well as the ensuing rate of decline in glomerular filtration rate: (index (glomerulopathy) vs rate of decline in glomerular filtration rater=0.84,p〈0.0001). No correlation was found between glomerular volume and the ensuing rate of decline in glomerular filtration rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02374500
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  • 7
    Electronic Resource
    Electronic Resource
    Glomerular epithelial foot processes and filtration slits in IDDM patients (1995)
    Springer
    Diabetologia 38 (1995), S. 1197-1204 
    Details
    ISSN: 1432-0428
    Keywords: Key words Albuminuria ; diabetic glomerulopathy ; diabetic nephropathy ; filtration slits ; glomerular epithelial cells ; stereology.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic nephropathy is associated with functional changes in the glomerular filtration barrier but the structural counterpart remains unknown. Width of glomerular epithelial cell foot processes and of filtration slits were determined by morphometric methods in 11 non-diabetic kidney donors and in 28 diabetic patients with albumin excretion rates ranging from normal to proteinuria. Foot process width was estimated from the ratio of tuft surface density to length density of slits. At high magnification independently sampled, perpendicularly cut slits were classified. Foot process width on peripheral basement membrane was increased in microalbuminuric compared to normoalbuminuric diabetic patients (p 〈 0.05) but showed no significant correlation with the level of albumin excretion when patients with increased barrier permeability were considered. Width of filtration slits in normo- and microalbuminuric diabetic patients exceeded that in non-diabetic control subjects (p 〈 0.05). Filtration slits were narrower in patients with overt proteinuria than in patients with microalbuminuria (p 〈 0.05) and correlated with glomerular filtration rate in all of the diabetic patients (r = 0.65, p 〈 0.005). The results show that insulin-dependent diabetic patients with nephropathy present changes of epithelial cells and filtration slits, demonstrable already in the stage of microalbuminuria. The mechanism of albumin leakage is not achieved by these measures. The dimension of filtration slits may play a contributing role in the level of glomerular filtration rate in diabetic patients. [Diabetologia (1995) 38: 1197–1204]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00422369
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  • 8
    Electronic Resource
    Electronic Resource
    Metabolic risk factors for cardiovascular disease in pancreas and kidney transplant recipients (1991)
    Springer
    Diabetologia 34 (1991), S. S44 
    Details
    ISSN: 1432-0428
    Keywords: Pancreas transplantation ; Serum lipoproteins ; Metabolic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyperinsulinaemia when combined with insulin resistance and hypertriglyceridaemia is a risk factor for cardiovascular disease. We have studied the serum lipid profile and glycaemic control in 27 uraemic diabetic patients, 23 Type 1 (insulin-dependent) diabetic kidney recipients, 18 non-diabetic kidney recipients, and 30 recipients of kidney and pancreas transplants at 6 months post-transplantation. Fasting serum triglycerides were increased in the uraemic diabetic patients and non-diabetic kidney transplanted patients but not in diabetic kidney transplanted patients whether or not they had received a pancreas. Total cholesterol was increased only in the uraemic diabetic patients while HDL cholesterol was normal in all groups. Whithin the pancreas and kidney transplanted group triglyceride values correlated with glomerular filtration rate (r=−0.55) but not with plasma insulin, glycated haemoglobin or kG-value following an intravenous glucose load. Plasma insulin was increased. Whether such isolated hyperinsulinaemia confers an increased risk of cardiovascular disease is not known. There may be adaptive feed-back mechanisms to protect target cells. Increasing the surgical risk in attempts to secure insulin delivery to the portal circulation does not seem warranted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00587617
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  • 9
    Electronic Resource
    Electronic Resource
    Glomerular epithelial foot processes and filtration slits in IDDM patients (1995)
    Springer
    Diabetologia 38 (1995), S. 1197-1204 
    Details
    ISSN: 1432-0428
    Keywords: Albuminuria ; diabetic glomerulopathy ; diabetic nephropathy ; filtration slits ; glomerular epithelial cells ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic nephropathy is associated with functional changes in the glomerular filtration barrier but the structural counterpart remains unknown. Width of glomerular epithelial cell foot processes and of filtration slits were determined by morphometric methods in 11 non-diabetic kidney donors and in 28 diabetic patients with albumin excretion rates ranging from normal to proteinuria. Foot process width was estimated from the ratio of tuft surface density to length density of slits. At high magnification independently sampled, perpendicularly cut slits were classified. Foot process width on peripheral basement membrane was increased in microalbuminuric compared to normoalbuminuric diabetic patients (p〈0.05) but showed no significant correlation with the level of albumin excretion when patients with increased barrier permeability were considered. Width of filtration slits in normo- and microalbuminuric diabetic patients exceeded that in non-diabetic control subjects (p〈0.05). Filtration slits were narrower in patients with overt proteinuria than in patients with microalbuminuria (p〈0.05) and correlated with glomerular filtration rate in all of the diabetic patients (r=0.65, p〈0.005). The results show that insulin-dependent diabetic patients with nephropathy present changes of epithelial cells and filtration slits, demonstrable already in the stage of microalbuminuria. The mechanism of albumin leakage is not achieved by these measures. The dimension of filtration slits may play a contributing role in the level of glomerular filtration rate in diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00422369
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  • 10
    Electronic Resource
    Electronic Resource
    Latent overhydration and nocturnal hypertension in diabetic nephropathy (1995)
    Springer
    Diabetologia 38 (1995), S. 216-220 
    Details
    ISSN: 1432-0428
    Keywords: Key words Insulin-dependent diabetes mellitus ; diabetic nephropathy ; ambulatory blood pressure ; circadian variation ; extracellular volume.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary With the aim of studying the diurnal variation in blood pressure in relation to degree of fluid retention, 24-h ambulatory blood pressure monitoring was performed in 31 insulin-dependent diabetic patients with nephropathy. The extracellular volume was calculated from the distribution volume of 51Cr-EDTA after a single injection. The study population was arbitrarily divided into two groups, depending on their extracellular volume. Group 1 included 15 patients with a lower extracellular volume and group 2, 16 patients with a higher extracellular volume. Ambulatory blood pressure was measured with a portable monitor using an oscillometric technique. In all patients, the mean ± SD 24-h ambulatory blood pressure was 135/79 ± 14/7 mm Hg. Day and night-time blood pressures were 136/81 ± 14/7 and 133/75 ± 17/8, respectively (p 〈 0.02). The ambulatory blood pressure was 135/80 ± 14/7 in group 1 and 136/78 ± 15/6 mm Hg in group 2. The nocturnal change in blood pressure was significantly greater in group 1 than in group 2, −9/−9 ± 10/5 mm Hg and 1/−3 ± 10/6 mm Hg, respectively (p = 0.005/0.01). There were no other significant differences between the groups than the diurnal blood pressure pattern. There were significant correlations between day ambulatory blood pressure and night ambulatory blood pressure and 24-h ambulatory blood pressure and urinary albumin excretion. There was no correlation between auscultatory clinic blood pressure on the one hand and albuminuria on the other. Latent fluid retention therefore may contribute to nocturnal hypertension in diabetic nephropathy. [Diabetologia (1995) 38: 216–220]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400097
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