We attempted to produce an experimental model of diabetic microangiopathy in rats by injections of streptozotocin (STZ) and 3, 3'-iminodipropionitrile (IDPN) and also investigated the preventive effects of 7-ethoxycarbonyl-4-hydroxymethyl-6, 8-dimethyl-1-(2H)-phthalazinone (EG 626), a new anti-platelet agent, on the animal model of diabetic microangiopathy. STZ (45 mg/kg i.v.) alone failed to produce retinopathy over five-month period, although it induced hyperglycemia. However, examination of trypsin-digested flat preparations of retinas in STZ-diabetic rats with IDPN (0.125-1.0 g/kg s.c.) revealed lesions such as degeneration of pericytes, capillary closure and microaneurysms. On the other hand, glomerular changes, such as basement membrane thickening, fibrin caps and glomerular capillary aneurysms, developed in STZ-diabetic rats with or without IDPN. The glomerular changes showed some similarity to those observed in humans. The effects of oral administration of EG 626 (100-400 mg/kg/day) for three or five months on the animal model are summarized as follows:(1) EG 626 suppressed the elevation of blood glucose levels caused by the injection of STZ. (2) EG 626 did not change the decrease of body weight after STZ. (3) EG 626 suppressed the incidence of cataracts after STZ. (4) EG 626 suppressed the increase in the wet weight of the kidney after STZ. (5) The incidence of retinal capillary lesions, such as degeneration of pericytes with STZ was suppressed by EG 626 in the flat retinal preparations. (6) The incidence of diabetic glomerular lesions, such as glomerular capillary aneurysms with STZ, was suppressed by EG 626. These findings indicate that EG 626 is a useful agent for the treatment of diabetic microangiopathy.

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The purpose of the present study was to investigate the effect of apple fiber (AF) on plasma lipoproteins and glucose tolerance in non-insulin dependent diabetic patients. Eleven diabetics (7 females and 4 males) ingested 5 or 15 g of AF per day for 6 months.
The total cholesterol level was reduced from 233 33 (mean±SD) mg/dl to 221±29 mg/dl by the addition of AF. Low density lipoprotein (LDL) ₂-cholesterol was significantly (p<O.05) reduced from 177±31 mg/dl to 161±32 mg/dl, and high density lipoprotein (HDL) 2-cholesterol was significantly (p<O.05) increased from 19.4±4.1 mg/dl to 24.8±4.6mg/dl. The ratio of HDL2-cholesterol to LDL₂-cholesterol, as an anti-atherogenic index, was significantly (p<O.01) increased from 0.11±0.03 to 0.16±O.06. The plasma triglyceride and lipoprotein-triglyceride levels did not change.
There was a decrement, although small, in the plasma glucose levels at 60 and 90 min and in the plasma insulin levels at O and 120 min during 75 g glucose tolerance test, by the addition of AF. The fasting plasma glucose level did not change.
These results suggest that AF may represent a useful adjuvant in the dietary management of diabetes, which may show a decreased incidence of diabetic macroangiopathy.

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To investigate the effects of sulfonylureas (SU) on long-term glycemic control, body weight control and vascular complications in patients with obese non-insulin dependent diabetes mellitus (o-NIDDM), 108 cases of o-NIDDM who were newly diagnosed and who underwent treatment for more than ten years in our clinic were studied retrospectively. Of them, 47 cases were on SU (Group SU) and 61 cases were on diet alone (Group D) for at least ten years. All patients were 10% or more above their ideal weight at the time of commencement of their treatment. Patients who reduced their body weight to levels of less than of 110% their ideal weight within five years were classified as the group with good weight control (weight controlled group).
The following results were obtained.
1) Significant reductions of both fasting plasma glucose levels and body weight were found in most cases of Group D within three years. On the other hand, in most cases of Group SU, reduction of the fasting plasma glucose levels was not accompanied by reduction of body weight.
2) Cases who were classified in the weight controlled group showed good glycemic control throughout the observation period. However, in cases not included in this group, a gradual increase in fasting plasma glucose levels was found during the last five years of the observation period.
3) The incidences of diabetic retinopathy at the seventh observation year were 38.3% in Group SU and 16.4% in Group D, and the difference between the groups was statistically significant (p<0.02). The incidences at the tenth observation year were 66.0% and 29.8%, respectively, and the difference was more highly significant (p<0.001).
4) In cases who showed good glycemic control (mean plasma glucose levels of less than 150mg/dl), the incidence of diabetic retinopathy was higher in cases who had failed in weight control as compared to those who were classified in the weight controlled group (56.0% vs. 8.7% p<0.001).
5) Irrespective of the method of treatment and the degree of glycemic control, the incidence of hypertension at the tenth observation year was higher in cases who had failed in weight control as compared to those who were classified in the weight controlled group (51.4% vs. 29.6%, p<0.05).
These results suggest that unsuccessful weight control in the treatment of o-NIDDM with SU may have some relation to the developmet of vascular complications.

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The spontaneously diabetic NOD (Non-Obese Diabetic) mouse has become an important animal model of Type 1 insulin-dependent diabetes mellitus.
60-70% of female and less than 20% of male NOD mice develop diabetes mellitus within 24 weeks of age associated with insulitis and destruction of B cells of the pancreas islets. The pathological changes in the organs of NOD mice were investigated in comparison with ICR mice as controls, between newborn and one and a half years old.
The body weight of the NOD mice was usually lower than that of the controls, mainly in the female. Histologically there was infiltration of lymphocytes in the thyroid glands, adrenal glands, salivary glands and testis, of which lymphocytic thyroiditis in male and lymphocytic infiltration of the salivary glands in female NOD mice were significantly more frequent than in the controls.
The weight of the spleen in the NOD mice was generally lower than in the controls, showing depletion of lyphocytes in both the T and B cell areas.
The size of the thymus was also smaller until 24 weeks of age. Histologically, the cortex was rapidly involuted in the early age, frequently associated with lymphoid follicles with germinal centers in the medulla.
An orthodiagnostic system revealed that the mean size of the thymocytes of the NOD mouse was smaller than that of the control mouse.
NOD mice were frequently associated with malignant tumors such as thymic leukemic. These results suggest that there may be a highly significant correlation between congenital abnormalities of the thymus and T lymphocytes in NOD mice.

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[in Japanese]

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Total body fat and its distribution pattern were assessed by a series of four (biceps triceps, subscapular and suprailiac) skinfold measurements in 180 non-insulin dependent diabetics.
Although females, both diabetic and nondiabetic, showed a significant increase in total body fat as compared to males, there was no significant difference between diabetics and nondiabetic controls matched for sex and relative body weight.
Diabetic subjects, however, revealed a significant centripetal or musculine type of distribution of body fat. Thus, the measurements in diabetics at the site of the biceps and the triceps were smaller, and those at the subscapular and suprailiac sites were larger than the measurements of controls.
Among the four skinfold measurements, the subscapular and suprailiac measurements showed the highest degree of correlation with changes in body weight and with fasting serum lipids, especially the triglyceride levels.
The above data suggest that the fat cells in the trunk region are more sensitive to metabolic factors than those in the arms, and the centripetal distribution of body fat observed in diabetics might be a reflection of some metabolic derangements in non-insulin dependent diabetes mellitus.

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The present study was undertaken to determine the effects, of Glibenclamide on plasma lipoprotein and postheparin lipolytic activity, i.e., plasma lipoprotein lipase (LPL) and hepatic lipase (HL), in rats. Twenty-four male rats of the Wistar strainweighing 200 g were divided into two groups. The first group was given a daily dosage of 2mg/kg of body weight of Glibenclamide suspended in 2% starch solution (G-group). The rats of the second group received 2% starch solution only (C-group). They were fed standard rat chow for eight
Cholesterol (C) and triglyceride (TG) levels of very-low-, low-and high-density lipoprotein (VLDL, LDL and HDL) were similar in both groups. The ratio of TG to C (TG/C) of VLDL in the G-group (16.5±1.9, mean±SD) was significantly lower (p<0.05) than that of the Cgroup (21.7±5.1). HL activity in the G-group (2.76±1.12μEq FFA/ml plasma/hour) was significantly lower (p<0.05) than that of the C-group (4.98±2.22μEq FFA/ml plasma/hour).However, LPL activity was similar in both groups.
These results suggest that Glibenclamide may lead to an accumulation of C-rich VLDL “atherogenic lipoprotein” which may be mediated by a decrement of HL activity.

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In an attempt to evaluate the role of selective α-adrenergic receptors on Langerhans' islet cells, insulin and glucagon secretion from rat isolated islets were determined with epinephrine, phenylephrine (α₁-stimulator), clonidine (α₂-stimulator), prazosin (α₁-blocker) and yohimbine (a₂-blocker). A new hypoglycemic drug, which was recently reported to act as a α₂ blocker, was also studied in, this connectin.
As already known, epinephrine (5μM) and clonidine (2μM) significantly inhibited insulin secretion and augmented glucagon secretion in the presence of low concentrations of glucoce (5-10 mM). I these conditions, when 100μM of prazosin were added, insulin secretion recovered well, but glucagon secretion was not affected. And when 100μM of yohimbine or DG 5128 were added, insulin or glucagon secretion was significantly increased or decreased, respectively, proving the blocking effect against epinephrine or clonidine. The dose-response curve of insulin and glucagon secreton induced by glucose (0, 5, 10, 15 and 20 mM) were shifted to the left in the presence of DG 5128 (100 and 200μM), changing the maximal response, namely, increaing insulin secretion in high glucose and decreasing glucagon secretion in low glucose.
Thus, glucagon as well as insulin secretion could be regulated mainly through α₂ adrenergic receptors in a tonic fashion. In addition, DG 5128, a new hypoglycemic drug, seems to act as a α₂ blocker in its effect on the glucose metabolism.

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