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Biomedical subjects

D Koya

Publications and source records attributed to D Koya.

11 recordsLinked to original sources

Glucose enhances type IV collagen production in cultured rat glomerular mesangial cells.

Type IV collagen production by cultured glomerular mesangial cells and the effect of glucose on it were evaluated in order to explore the possible contribution of mesangial cells to the accumulation of type IV collagen in mesangial matrix typically seen in diabetes. Type IV collagen was measured quantitatively by enzyme-linked immuno-sorbent assay. The majority of type IV collagen was secreted into culture media and secreted-type IV collagen increased with cell growth in early log phase and decreased in late log phase and after confluency. By exposing the cells to high concentrations of glucose (27.8 mmol/l), both secreted- and cell-associated-type IV collagens increased significantly compared with the cells cultured under normal glucose concentrations (5.6 mmol/l) or under equivalent concentrations of mannitol, resulting in a significant increase in total type IV collagen accumulation from 32.1 +/- 6.4 (under 5.6 mmol/l glucose) to 51.0 +/- 4.6 micrograms/dish (mean +/- SD, n = 4) on day 4, from 113.6 +/- 6.6 to 156.8 +/- 7.1 on day 6, from 248.5 +/- 15.2 to 310.0 +/- 12.6 on day 8 and from 372.4 +/- 14.8 to 507.9 +/- 17.2 on day 12. These results indicate the importance of glucose-induced alteration of mesangial cell function in the development of diabetic mesangial expansion.

Animals

Metabolic actions of insulin-like growth factor I in cultured glomerular mesangial cells.

Glomerular mesangial cells in culture have been reported to possess a considerable number of receptors specific to insulin-like growth factor I (IGF-I), with very small number of receptors specific to insulin. To explore acute metabolic effects of IGF-I on mesangial cells, uptake of glucose and amino acid was measured in the presence of IGF-I or insulin. IGF-I stimulated D-[U-14C]glucose incorporation, 2-deoxy[1-3H]glucose uptake and alpha-[methyl-3H]aminoisobutyric acid (AIB) uptake into cultured mesangial cells by 139.8% +/- 2.1%, 116.6% +/- 1.7%, and 214.9% +/- 12.8% (percent of basal), respectively. Similar maximal stimulation was also induced by insulin, while the ED50 of IGF-I to stimulate these uptake systems (9.98 +/- 2.36, 3.45 +/- 1.86, and 3.35 +/- 0.40 ng/mL, respectively) was significantly lower than that of insulin (120.8 +/- 28.5, 61.8 +/- 7.7, and 76.3 +/- 17.5, respectively). These results indicate that, in cultured glomerular mesangial cells, IGF-I induces acute metabolic effects, possibly through its own receptors.

Amino Acids

Dual mechanism of angiotensin II inhibits ANP-induced mesangial cGMP accumulation.

To evaluate an interaction between vasoconstrictive (Ang II) and vasodilating (ANP) peptides, we examined the effect of Ang II on ANP-induced accumulation of cGMP in cultured glomerular mesangial cells. ANP rapidly increased intracellular cGMP levels, with a peak stimulation at one minute in the absence of IBMX and at ten minutes in the presence of IBMX. The ANP-induced cGMP accumulation was significantly inhibited when the cells were treated with Ang II simultaneously with ANP for one minute in the absence of IBMX. This inhibitory effect of Ang II was completely abolished by IBMX and significantly reduced in calcium-free media or by W7, but not affected by H7. Similar inhibitory effect was observed when cells were treated with A23187 but not with TPA for one minute. In the presence of IBMX, Ang II inhibited ANP-induced cGMP accumulation when cells were treated with Ang II for 15 minutes prior to the stimulation by ANP. This inhibition by Ang II was blocked by H7. ANP-induced increase in particulate guanylate cyclase activity was significantly reduced in the cells treated with Ang II or TPA. This reduction of enzyme activity was also prevented by H7. These results indicate that Ang II inhibits ANP-induced cGMP accumulation in cultured glomerular mesangial cells through at least two mechanisms; one is the activation of calcium-dependent, calmodulin-stimulated cyclic nucleotide phosphodiesterase in the initial phase, and the other is the inhibition of guanylate cyclase resulting from protein kinase C activation in the maintenance phase.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Cutaneous manifestations of gastrointestinal disease.

Numerous diseases affect the skin and gut simultaneously. The early recognition and treatment of both components is often essential to decrease morbidity and even prevent death precipitated by gastrointestinal crises. A number of the diseases affecting both the skin and gut are discussed, with particular emphasis on recent developments.

Acrodermatitis

Microalbuminuria associated with a rise in blood pressure in non-insulin-dependent diabetes.

The association between microalbuminuria and systemic blood pressure was investigated in 80 nonproteinuric subjects with non-insulin-dependent diabetes. Seventeen of 80 diabetics had urinary albumin excretion rates (AER) over 20 micrograms/min and were defined as microalbuminuric. The microalbuminuric diabetics showed a higher incidence of proliferative retinopathy and neuropathy than the normoalbuminurics. Moreover, the former group had significantly higher values of systolic blood pressure compared to the latter, although the creatinine clearance was not significantly different between the two groups. These results suggest that microalbuminuria is strongly associated with a rise of systemic blood pressure in non-insulin-dependent diabetics.

Albuminuria

Insulin-like growth factor I (IGF-I) stimulates glucose and amino acid uptake in cultured glomerular mesangial cells.

Cultured mesangial cells possess a large number of receptors specific to IGF-I with a small number of insulin receptors. Physiological concentrations of IGF-I increased the uptakes of aminoisobutyric acid and 2-deoxyglucose in mesangial cells, while insulin exhibited similar effects only with unphysiologically high concentration. These findings suggest that, in cultured mesangial cells, IGF-I may regulate cellular metabolic functions such as glucose and amino acid uptakes through its own receptors rather than insulin receptors.

Aminoisobutyric Acids

Glucose-induced overproduction of type IV collagen in cultured glomerular mesangial cells.

Type IV collagen production by cultured rat glomerular mesangial cells was evaluated quantitatively by measuring type IV collagen secreted into culture media and associated with the cells using enzyme-linked immunosorbent assay (ELISA). The majority of type IV collagen was secreted into culture media; type IV collagen increased with cell growth in the early log phase and decreased in the late log phase and after cofluency. By exposing the cells to high concentrations of glucose (27.8 mM), both secreted and cell-associated type IV collagens increased significantly compared with the cells cultured under normal glucose concentrations (5.6 mM) or under equivalent concentrations of mannitol, resulting in a significant increase in total type IV collagen accumulation.

Animals

Reduced activity of renal angiotensin-converting enzyme in streptozotocin-induced diabetic rats.

To clarify the possible role of intrarenal renin-angiotensin system (RAS) in the evolution of renal hemodynamic alteration in diabetes, we investigated the change of tissue angiotensin-converting enzyme (ACE) activity, a key enzyme of RAS, in the kidneys obtained from streptozotocin-induced diabetic rats. Tissue ACE activity was significantly reduced in both outer cortex (0.29 +/- 0.04, mean +/- SEM, n = 6) and inner cortex with outer medulla (2.43 +/- 0.28, n = 6) of the kidneys from diabetic rats 2 weeks after induction of diabetes compared with those from control rats (0.47 +/- 0.05, n = 7, in outer cortex; 3.68 +/- 0.32, n = 7, in inner cortex with outer medulla). ACE activities in the lung and aorta of diabetic rats were not different from those of control rats. ACE activities in the serum and urine were significantly elevated in diabetic rats. Treatment of diabetic rats with insulin to achieve near euglycemia completely prevented these alterations in ACE activity, except that, in the urine, the elevation of ACE was partially corrected with insulin. In contrast to ACE activity, activity of N-acetyl-beta-D-glucosaminidase (a lysosomal enzyme of the tubule) and r-glutamyl transpeptidase (a brush border enzyme) in the kidney were not reduced in diabetic rats, whereas in the urine both enzyme activities were significantly elevated in diabetic rats. It is likely, therefore, that the reduction of ACE activity in the kidneys of diabetic rats may reflect the impairment of vascular endothelial cells in the kidney, rather than tubular damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase

High blood pressure is a risk factor for the development of microalbuminuria in Japanese subjects with non-insulin-dependent diabetes mellitus.

In this study, 52 nonproteinuric Japanese patients with non-insulin-dependent diabetes (NIDDM) were followed from 1985 to 1990 to investigate the rate of development and progression of microalbuminuria and the factors which influence it. In 1985, 34 patients were normoalbuminuric, and 18 patients were microalbuminuric. Five years later, 11 of 34 initially normoalbuminuric patients (32.4%) developed microalbuminuria, and 6 of 18 initially microalbuminuric patients (33.3%) developed overt proteinuria. At the beginning of the study, hypertension existed more frequently in the patients who later developed microalbuminuria (8 of 11, 72.7%) than in the patients who stayed normoalbuminuric (4 of 23, 17.4%). Age-adjusted values of mean blood pressure (+/- SEM) at the beginning of the study in the patients who developed microalbuminuria (98.2 +/- 3.4 mm Hg, n = 11) were significantly higher than those in the patients who stayed normoalbuminuric (87.3 +/- 2.4 mm Hg, n = 23). In six patients who developed overt proteinuria, initial urinary albumin excretion rates (AER) were higher than those in the patients who stayed microalbuminuric, and four patients who presented with initial AER greater than 100 micrograms/min all developed overt proteinuria. These results indicate that, in Japanese patients with NIDDM, the rate of development of microalbuminuria is faster than that reported in Caucasian IDDM, and preexisting hypertension with relatively poor control of blood pressure may be a risk factor for the development of microalbuminuria.

Adult