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Biomedical subjects

T Kazumi

Publications and source records attributed to T Kazumi.

At least 73 records · Page 4Linked to original sources
PubMed1989

Protective effect of probucol on alloxan diabetes in rats.

The diabetogenic action of alloxan is known to be attenuated by several oxygen radical scavengers. The present study was conducted to see if probucol, a drug with strong free radical scavenger action, can reduce pancreatic B-cell damage induced by alloxan in male Wistar rats. After 2 weeks of a 1% probucol diet, 50 mg/kg alloxan was intravenously injected in rats (group PA, n = 34). Urine glucose of most of the injected rats not pretreated with probucol (group A, n = 22) was positive, while more than half of the rats of group PA failed to show urine glucose. The blood glucose level in group PA was significantly lower than that in group A (326 +/- 25 vs. 487 +/- 28 mg/dl, P less than 0.001). Histological examination revealed that most of the pancreatic islets of group A were degranulated, whereas a lot of islets remained unaffected in group PA. Thus, the in vivo diabetogenic action of alloxan was reduced by pretreatment with probucol, although the effect was incomplete. This effect can be explained by probucol's strong free radical scavenger action. Since accumulation of free radicals can be an initial step of B-cell damage in animal models of type 1 (insulin-dependent) diabetes, the drug can be useful for the prevention of type 1 diabetes with its long-term clinical history of safety.

Alloxan↗
PubMed1989

Estimation of cholesterol loading of the low-density lipoprotein fraction in diabetic subjects without ultracentrifugation.

We report here a new formula for estimating apolipoprotein (apo) B concentration in the low-density lipoprotein (LDL) fraction from measurements of plasma triglyceride and apoB. ApoB in plasma and in the triglyceride-rich lipoprotein fraction (VLDL, d less than 1.019) and plasma triglyceride were measured in 112 subjects, including 56 diabetics. There was a significant correlation between VLDL-apoB and plasma triglyceride (Y = 0.07X + 1, r = 0.73, P less than 0.001). We calculated LDL-apoB according to this formula: LDL-apoB = total apoB - (0.07 x total triglyceride + 1). We found an excellent relationship between LDL-apoB (total apoB - VLDL-apoB) and calculated LDL-apoB (Y = 1.0X + 1, r = 0.96, P less than 0.001). This new formula will enable us to estimate the apoB concentration in the LDL fraction without ultracentrifugation.

Apolipoproteins B↗
PubMed1989

Effects of dietary sucrose on age-related changes in VLDL-triglyceride kinetics in the rat.

The effects of sucrose feeding on in vivo kinetics of triglyceride metabolism were compared in rats aged 2 and 12 months. Sucrose was supplied as a 10% solution in their drinking water for 2 weeks. Although plasma triglyceride concentrations doubled with age, total triglyceride secretion rates for the whole rat (mg/min/rat) increased by 40%, suggesting a decrease in the efficiency of triglyceride removal from plasma with aging. The rate of triglyceride secretion per unit body mass (mg/min/kg body weight), however, decreased by 40% as the rats grew to 12 months of age. These age-related differences were statistically significant only in rats receiving supplementary sucrose. Feeding sucrose to rats of both ages doubled the secretion rates of triglyceride not only for the whole rat but also per unit body mass. However, it tripled triglyceride concentrations, implying that the sugar decreases the removal efficiency of plasma triglyceride equally in rats at either age. Fasting hypertriglyceridemia induced by sucrose supplement was much greater in old rats than in young rats (162 +/- 30 vs. 80 +/- 8 mg/dl). The present studies demonstrate that dietary sucrose enhances age-related changes in triglyceride kinetics in the rat.

Aging↗
PubMed1989

Combined effect of exogenous insulin and sucrose on alterations in plasma lipoproteins induced by cholesterol feeding in the rat.

We have recently reported increased cholesterol concentrations in high-density and very-low-density lipoproteins (HDL and VLDL) in sucrose-fed rats with exogenous hyperinsulinemia. In order to see if exogenous hyperinsulinemia has any effect on the alterations in plasma lipoproteins induced by cholesterol feeding, we fed a cholesterol-rich diet supplemented with lard, cholic acid and propylthiouracil to hyperinsulinemic, sucrose-supplemented rats and examined plasma lipoprotein profiles. Three control groups were investigated: one receiving chow only, the other receiving a cholesterol-rich diet, the third receiving exogenous insulin, sucrose, and no cholesterol-rich diet but chow. Hyperinsulinemia was induced by a constant s.c. infusion of porcine insulin (6 U/day) from an osmotic minipump. Insulin infusion plus sucrose produced an increase in HDL cholesterol concentrations similar to that seen in the previously reported injection model in the face of no change in total and low-density lipoprotein (LDL) cholesterol. Rats receiving a cholesterol-rich diet but no insulin developed marked hypercholesterolemia characterized by an elevation of cholesterol not only in LDL but also in intermediate-density lipoprotein (IDL) and VLDL. Infusing insulin into cholesterol-fed rats produced a further increase in IDL and VLDL cholesterol but was not accompanied by any further increase in LDL cholesterol. HDL cholesterol was decreased below normal.

Animals↗
PubMed1989

Effect of dietary fructose on triglyceride turnover in streptozotocin-diabetic rats.

The effects of fructose or glucose on plasma triglyceride kinetics in streptozotocin (40 mg/kg) diabetic rats were studied using Triton WR1339. To separate groups of diabetic rats fructose or glucose was supplied at 10% in drinking water. Diabetic rats without sugar supplementation (diabetic control) had significantly suppressed triglyceride secretion compared to non-diabetic controls. Neither fructose nor glucose supplementation increased the triglyceride secretion rate in diabetic rats. However, despite reduced secretion rates, plasma triglyceride levels in glucose-supplemented diabetic rats, diabetic controls and non-diabetic controls were essentially identical. This suggested that removal of triglyceride from the circulation was impaired in the diabetic rats. In contrast, fructose supplementation resulted in a more than 150% (significant) increase in the mean plasma triglyceride of diabetic rats. The observation of significant hypertriglyceridemia in spite of low triglyceride secretion rate in fructose-supplemented diabetic rats suggests that dietary fructose, but not glucose, interferes with triglyceride removal from the circulation of streptozotocin-diabetic rats. This impairment by dietary fructose is in addition to the impaired triglyceride removal associated with diabetes alone.

Animals↗
PubMed1989

Long-term treatment of hypercholesterolemic non-insulin dependent diabetics (NIDDM) with pravastatin (CS-514).

We examined the long-term effect of pravastatin, a new potent inhibitor of endogenous cholesterol biosynthesis, on glucose and lipid metabolism in hyperlipidemic NIDDM. Ten patients (5 on sulfonylurea, 5 on diet) were studied over 12 months. Five were WHO type IIa and 5 were type IIb. Blood was taken before and then 1, 6 and 12 months after initiating 10 or 20 mg daily of pravastatin. The cholesterol concentration in whole plasma and very low density lipoprotein (VLDL), plasma triglyceride and apolipoprotein (apo) B were all significantly decreased within the first month. These changes lasted for 1 year. High density lipoprotein (HDL)-cholesterol increased in the first month but returned to base line thereafter. Low density lipoprotein (LDL)-cholesterol tended to decrease in the first month, and was suppressed significantly from the 6th month (11%) to the 12th month (16%). The effect of pravastatin on LDL-cholesterol in NIDDM was slower and weaker than that published for non-diabetic hypercholesterolemia. Therefore, the mechanism by which pravastatin suppresses plasma cholesterol levels in these two conditions may differ. After 1 year, no adverse effects were noted on hematopoietic, hepatic or renal function. Blood glucose level, hemoglobin A1c and the insulin response to oral glucose were unchanged. In addition, serum creatine phosphokinase showed no abnormal increase. Careful ophthalmological examinations before and after pravastatin treatment revealed no development of new lenticular opacities. Thus, pravastatin appears to be a safe and effective drug for the long-term treatment of NIDDM with hypercholesterolemia.

Adult↗
PubMed1989

The role of insulin in triglyceride turnover in rats.

Exogenously induced hyperinsulinemia can increase in vivo triglyceride production in rats receiving dietary fructose, either as monosaccharide or as sucrose, but not in those receiving only glucose. Thus, in the presence of fructose, but not glucose, insulin stimulates triglyceride production. Dietary fructose can also impair the removal of circulating triglyceride. Exogenous insulin overcomes this fructose-associated impairment of triglyceride removal. On the other hand, streptozotocin-diabetic rats showed a suppressed triglyceride secretion rate (TgSR) but their plasma triglyceride level was unchanged. Therefore, insulin deficiency may result in not only decreased production of triglyceride but also impaired triglyceride removal from the circulation. Fructose-fed diabetic rats showed higher plasma triglyceride levels than chow-fed diabetic rats without a concomitant increase in TgSR, suggesting impaired triglyceride removal from the circulation induced by fructose in diabetic rats. Glucose-fed diabetic rats did not differ in TgSR or plasma triglyceride level from chow-fed diabetic rats. These observations indicate that circulating insulin and dietary fructose, but not glucose, have a key role in very-low-density lipoprotein triglyceride turnover in rats.

Animals↗
PubMed1988

Effect of CS-514 (pravastatin) on VLDL-triglyceride kinetics in rats.

The effect of CS-514 (pravastatin; Sankyo Co., Tokyo), a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, on triglyceride turnover, was studied in male Wistar rats. CS-514 (15 +/- 1 mg/day per rat) was administered as a 0.04% solution in drinking water for 14 days. Triglyceride and cholesterol in very low density lipoprotein (VLDL) and plasma triglyceride were reduced by treatment with CS-514. Plasma cholesterol level was not suppressed by CS-514. The CS-514 treated rats had a significantly suppressed triglyceride secretion rate (TgSR) during the fed state compared to control rats (0.85 +/- 0.1 vs. 1.07 +/- 0.3 mg/min, P less than 0.05). By contrast, CS-514 treatment did not suppress TgSR after an overnight fast. These data demonstrate that CS-514, an inhibitor of cholesterol biosynthesis can suppress VLDL-triglyceride secretion in rats and that this effect can be modified by dietary manipulation.

Animals↗
PubMed1988

Effects of CS-514 on plasma lipids and lipoprotein composition in hypercholesterolemic subjects.

The effect of CS-514 (eptastatin, Sankyo Co., Tokyo), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was investigated in 47 patients with hypercholesterolemia (WHO type IIa: 27, IIb: 20). Ten or 20 mg of CS-514 was administered daily for 3 months. In both types of patient, total cholesterol and phospholipid levels were significantly reduced by CS-514. The triglyceride, cholesterol and phospholipid content of low density lipoprotein (LDL) and the plasma levels of apolipoprotein B were also decreased in both groups. In contrast, total triglyceride, very low density lipoprotein (VLDL)-triglyceride and apolipoprotein C-II were decreased only in type IIb subjects. Also the levels of high density lipoprotein (HDL)-cholesterol and apolipoproteins A-I and A-II were increased by CS-514 in IIb but not in IIa patients. In both groups, no change occurred in either the cholesterol/triglyceride or phospholipid ratio in any lipoprotein fraction, nor in the ratio of HDL-cholesterol to apolipoprotein A-I or A-II, respectively. Therefore, CS-514 suppresses plasma levels of cholesterol in hypercholesterolemic patients without modifying lipoprotein composition. Moreover, this drug has different effects on the levels of plasma triglyceride and HDL-cholesterol of type IIa and IIb patients.

Adult↗
PubMed1987

Increased cholesterol concentration in intermediate density lipoprotein fraction of normolipidemic non-insulin-dependent diabetics.

There is increasing agreement about the atherogenicity of intermediate density lipoprotein (IDL). In order to determine whether normocholesterolemic diabetics are at a higher risk of atherosclerosis, cholesterol concentrations in three subclasses of triglyceride-rich lipoprotein fraction (Sf 12-400) were examined. Their plasma triglyceride and cholesterol levels were limited to below 150 and 250 mg/dl, respectively. They were divided into 3 groups according to their treatment: insulin injection (group I), sulphonylurea (group S) and diet alone (group D). Age-matched healthy normolipidemic non-obese subjects served as controls (group C). Triglyceride-rich lipoproteins were separated by ultracentrifugation: very low density lipoprotein (VLDL), Sf 60-400; intermediate density lipoprotein (IDL1), Sf 20-60; IDL2; Sf 12-20. Cholesterol concentrations in total plasma, VLDL, IDL2 and high density lipoprotein (HDL) were all identical in every group. A significant increase in cholesterol concentration was found in IDL1 of groups S and D. Low density lipoprotein-cholesterol of group I was also increased. These findings indicate an increased risk factor in normolipidemic diabetics.

Adult↗
PubMed1986

Portal v peripheral hyperinsulinemia and very low density lipoprotein triglyceride kinetics.

The effect of subcutaneously delivered insulin on the kinetics of rat plasma triglycerides was compared to that of intraperitoneally delivered insulin. The former route delivered insulin primarily extrahepatically and the latter, intraportally. In comparison to the intraperitoneally delivered insulin, the subcutaneously delivered insulin was associated with a higher peripheral serum insulin, lower serum glucose, lower serum FFA, lower serum triglycerides, and similar rate of triglyceride secretion. The activity of adipose tissue lipoprotein lipase was directly related to the serum insulin concentration. The pattern of serum triglycerides and lipoprotein lipase in the rats receiving subcutaneous insulin suggested that their rate of triglyceride removal exceeded that seen in the rats receiving intraperitoneal insulin. These observations indicate that the route of insulin delivery can influence the balance between the hepatic and extrahepatic effects of insulin on triglyceride kinetics.

Adipose Tissue↗
PubMed1986

Effect of CS-514, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on lipoprotein and apolipoprotein in plasma of hypercholesterolemic diabetics.

CS-514, one of the derivatives of ML-236B which is an inhibitor of endogenous cholesterol synthesis, has been previously shown to effectively reduce low density lipoprotein (LDL) cholesterol in dogs, rabbits and humans. We determined the effect of CS-514 on glucose, lipid, lipoprotein and apolipoprotein (apo) levels in plasma of 8 hypercholesterolemic diabetics (2 males). Total and LDL cholesterol and apo B levels were significantly decreased (P less than 0.005) 3 months after CS-514 treatment. High density lipoprotein (HDL) cholesterol was increased (P less than 0.05). Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) did not change throughout the observation period. No clinically serious adverse effects were experienced by the patients. We conclude that CS-514 can be a useful drug in the treatment of hypercholesterolemic diabetics and is remarkably free of any evidence of toxicity or unwanted side effects even in diabetics.

Apolipoproteins↗
PubMed1986

Thyrotropin-releasing hormone and insulin in chemically induced pancreatic islet cell tumors in rats.

Thyrotropin-releasing hormone (TRH) and insulin were measured by radioimmunoassay in acetic-acid extracts of 19 pancreatic islet cell tumors induced by streptozotocin and nicotinamide in rats. In addition, gel filtration properties of TRH-immunoreactivity and immunoreactive insulin (IRI) were examined in 5 and 14 tumors, respectively. TRH was demonstrated in 10 of 19 tumors, with a mean of 166 +/- 47 (SEM) pg/mg wet weight, whereas the concentration was less than 3 pg/mg wet weight in the other tumors. In contrast, all tumors contained IRI, with a mean of 11.0 +/- 1.6 micrograms/mg wet weight. Ten tumors in which TRH was demonstrated contained more IRI than those in which TRH was not detected (13.1 +/- 1.8 vs 6.5 +/- 1.7 micrograms/mg wet weight, P less than 0.02). After gel filtration, all TRH immunoreactivity was eluted at the same place as synthetic TRH in the 5 tumors. In addition, gel filtration elutes showed essentially the same pattern of IRI in the 14 tumors, with 3 peaks. The predominant IRI peak comigrated with marker insulin (95.7 +/- 0.8%), another prominent peak occurred coincident with proinsulin standard (3.3 +/- 0.5%), a third peak was present in the void volume (0.28 +/- 0.04%). These distributions of IRI were similar to those in extracts of normal pancreases. The present studies demonstrate TRH immunoreactivity in pancreatic islet cell tumors induced by streptozotocin and nicotinamide in rats. Chemically induced insulinomas can serve as a model for insulin storage which is analogous to islet B cells.

Adenoma, Islet Cell↗