Water-in-oil-in-water (W/O/W) insulin micelles were prepared, and the possibility of insulin absorption in a micellar form was examined. In this preparation, insulin was trapped in oil droplets of oleic acid in glyceryl-alpha-monooleate. (1) W/O/W insulin micelles were absorbed from the ligated jejunal loop of rabbits to the order of 12.3 to 58.5% of the dose given (10 mU/kg body weight) during the 3-h experimental period. (2) Alloxan diabetic rats were treated with intrajejunal administration of W/O/W insulin micelles at a dosage of either 25 or 50 mU/100 g body weight, three times daily for as long as 14 days. During treatment, a significant reduction in the daily excretion of urinary glucose was observed, concomitant with a decrease in fasting blood glucose. Quantitative estimates suggested that the effectiveness of 25 mU/100 g of intrajejunal W/O/W insulin micelles was comparable to that of regular insulin at a dosage of 1 mU/100 g i.m. These results would indicate that W/O/W insulin micelles, when given enterally, are more effective in lowering blood and urinary glucose levels than W/O/W insulin emulsions in which insulin was trapped in oil droplets of triglyceride.

Animals↗

PubMedDate not supplied

Validation of I.V. small-dose insulin infusion therapy in diabetic ketoacidosis of depancreatized dogs.

A validation of small-dose insulin infusion therapy was studied by the constant i.v. infusion of various doses of insulin into ketoacidotic depancreatized dogs. Constant insulin infusion of 5 x B, 10 X B, 30 X B and 50 X B (B = 225 microunit/kg/min) was performed for 3 h by mechanical pump. The following results were obtained: (1) plasma concentrations of immunoreactive insulin (IRI) increased proportionally to the dose of infused insulin, but the higher IRI did not result in a greater fall in plasma glucose concentration, correspondingly; the mean rate of fall in plasma glucose concentration of 5 x B was not significantly lower than that of 50 x B; beta-hydroxybutyrate and arterial pH improvements were observed in each group during the 3-h insulin infusion. These data suggested that for the improvement of diabetic ketoacidosis, the insulin infusion rate of more than 30 x B, which raised the plasma IRI levels above the physiological range, was not essential; (2) the necessity of potassium supplementation during the small-dose insulin infusion was suggested if the pre-treatment level of serum potassium was low. These results confirmed that in the absence of infection or severe acidosis small-dose insulin infusion therapy is as effective as the conventional large-dose insulin therapy.

Animals↗

PubMedDate not supplied

Morphological characteristics of dermal diabetic microangiopathy.

In an attempt to characterize dermal diabetic microangiopathy, dermal microvessels were qualitatively and quantitatively assessed in 26 healthy control subjects and 47 non-insulin-dependent diabetic patients. Basement membrane thickness (BMT) was significantly greater and the homogeneous BM more frequent in diabetic than in control microvessels. BMT did not change with duration of diabetes but significantly decreased with age and onset age of diabetes, suggesting either a different process of BM thickening with respect to age in diabetic dermal microvessels or the implication of genetic influence on the pathogenesis of dermal diabetic microangiopathy. Endothelial cell hyperplasia was not noted in dermal diabetic microvessels. In view of the fact that the hyperplasia has been reported in other tissues and is closely associated with diabetic microangiopathy, the nature of dermal microvessels or endothelial cells or the milieu around dermal microvessels might be different from other organs.

Basement Membrane↗

PubMedDate not supplied

Alcohol dehydrogenase: a new sensitive marker of hepatic centrilobular damage.

To determine whether serum alcohol dehydrogenase (ADH) activity reflects hepatic damage of centrilobular region (zone 3), the rats were given either bromobenzene (BB) or allyl alcohol (AA) IP to produce the pericen tral or periportal necrosis respectively. After AA or BB serum alanine aminotransferase (ALT) activity showed no significant difference between the two groups. By contrast, serum ADH and glutamate dehydrogenase (GLDH) activities were elevated preferentially in the BB treated rats. However, AA administration to rats also resulted in a significant increase in GLDH activity, whereas ADH activity was only slightly elevated when compared to controls. Moreover, acute ethanol administration to rats resulted in a significant elevation of the serum ADH activity, whereas serum GLDH and ALT activities remained normal. These data suggest that serum ADH activity appears to be a sensitive and specific marker of hepatic centrilobular damage.

1-Propanol↗

PubMedDate not supplied

Mild but prolonged elevation of serum angiotensin converting enzyme (ACE) activity in alcoholics.

Serum activity of angiotensin converting enzyme (ACE) was serially measured in 47 hospitalized chronic alcoholics with liver disease. Compared to healthy controls, ACE activity, on admission, in the serum of alcoholics was significantly elevated (42.5 +/- 16.6 U/ml vs. 32.4 +/- 9.6 U/ml; p less than 0.005). About 36% of the patients had an elevated ACE level exceeding an upper normal value of 42 U/ml (mean +/- SD). In contrast to the rapid normalization of such enzymes as aspartate transaminase (AST), alanine transaminase (ALT) and lactic dehydrogenase (LDH) which represent parenchymal liver cell injury, the activity of ACE remained elevated over a period of 4 weeks even with abstinence. The serum level of ACE was significantly correlated with levels of alkaline phosphatase, gamma-glutamyltranspeptidase and monoamine oxidase, but not with those of AST, ALT and LDH. These data suggest increased ACE activity in alcoholics may be related to the influence of chronic consumption of alcohol on hepatic nonparenchymal systems.

Adult↗

PubMedDate not supplied

Increase in mitochondrial GOT (m-GOT) activity after chronic alcohol consumption: clinical and experimental observations.

In order to clarify the origin and the mechanism of increased serum activity of glutamic oxalacetic transaminase (GOT) in chronic alcoholics, clinical and experimental investigations were carried out. Mitochondrial (m-GOT) and cytosolic GOT (c-GOT) isoenzymes were separated chromatographically by using a mini-column packed with Sephadex A50. Sixty percent of 63 alcoholics had elevated serum GOT. The m-GOT activity in alcoholics with total serum GOT activity of over 50 Karmen Units was 17.2 +/- 1.6 K.U. and the m-GOT/GOT ratio was the highest when compared to those in non-alcoholic liver diseases. In in vitro study, six hours of incubation of isolated hepatocytes from rats fed ethanol chronically resulted in an increased leakage of m-GOT into the incubation medium and also showed a tendency of a higher m-GOT/GOT ratio than that from control rats. The m-GOT activity thus released into the medium showed a highly significant inverse correlation with the viability of hepatocytes. These data suggest that m-GOT substantially contributes to an increased serum GOT often observed in chronic alcoholics.

Alcoholism↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Mesangial cell dysfunction.

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Animals↗

PubMedDate not supplied

Clinical significance of microalbuminuria in Japanese subjects with non-insulin-dependent diabetes.

In order to elucidate the clinical significance of microalbuminuria in non-insulin-dependent diabetes mellitus (NIDDM), 62 Japanese subjects with NIDDM and without proteinuria were followed for three years. After the three-year follow up, four (19%) of 21 microalbuminuric patients--albumin excretion rates (AER) greater than 15 micrograms/min--developed overt proteinuria, while none of the 42 normoalbuminuric patients did. Among these normoalbuminuric patients, eight patients (19.5%) developed microalbuminuria. The microalbuminuric patients who developed overt proteinuria had higher AER at the beginning of the study than the patients who stayed microalbuminuric. The patients who developed microalbuminuria showed a significantly higher systolic blood pressure in the final year than the patients who stayed normoalbuminuric. These results indicate that microalbuminuria precedes overt proteinuria in Japanese NIDDM, and progression of diabetic nephropathy is rapid and associated with a rise in blood pressure.

Albuminuria↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗