We observed 1390 diabetic cases (males 875, females 515) and 175 renal glycosuria cases (males 142, females 33) who were treated between 1960-1973.
We could determine the cause of death of 118 diabetics as follows : heart disease 24, cerebral hemorrhagia 12, cerebral thrombosis 12, cancer 22, diabetes 17, uremia 9, liver disease 6, infection 3 etc.
Retinopathia diabetica was observed in 1/3 of the diabetics and especially it was observed in diabetics with high FBS, and the mortality rate from retinopathia diabetica was two times that of nonretinopathia.
The percentage of therapy given to diabetics was as follows : diet therapy 50%, oral medicine 40%, insulin 10%. But from our observation during many years, the percentage of diabetics who were treated with insulin only for a short time or for a long time, increased to 20% and the percentage of diabetics who were treated with oral medicine only for a short time or for a long time and without insulin, increaied to 50%.
The mortality rate of diabetics who were treated with insulin was high.
Regarding the blood pressure, 71% of diebetics was normal, 14% of them showed continuous hypertension.
Regarding the albuminuria, 54% of diabetics was negative, 16% of them showed continuous albuminuria.
GTT of diabetics after a few days' treatment with a standard diet will be very useful to decide the grade of diabetes mellitus.

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After the administration of sulfonylurea (glibenclamide and tolbutamide), insulin and blood glucose were estimated in the normal subjects and diabetics.
In the normal group glibenclamide (5 mg) caused a tendency to decrease more markedly and maintain a lower level on blood glucose than tolbutamide (2.0g) after 120 minutes. While in the mild and moderate diabetic groups the blood glucose gradually lowered within 180 minutes after the administration of both glibenclamide and tolbutamide, although the lowering effect by glibenclamide was more remarkable in the moderate diabetic group. The increase of MI secretion by glibenclamide was later in reaching a peak and then lasted longer than by tolbutamide in the normal group. In the diabetic groups, no significant increase of IRI was observed both by glibenclamide and tolbutamide. In the normal group glibenclamide caused a tendency to gradually elevate the plasma NEFA value for 180 minutes. On the contrary, in the moderate diabetic group it caused a tendency to continuously decrease during that time. These findings were also observed by the administration of tolbutamide. No qualitative dif-ference between glibenclamide and tolbutamide was observed.
When a 50 g glucose load, preceded by the administration of glibenclamide, was carried out, the increases of insulinogenic index, half an hour after the glucose load, were significantly marked in the normal and mild diabetic groups, in comparison with the insulinogenic index on the glucose load only. A tendency to increase was also observed in the moderate diabetic group. While in the case of tolbutamide, that increase was significantly marked only in the normal group. Judging from these findings, it was suggested that the initial insulin secretion from β-cells to glucose load was increased by the previous administration of glibenclamide or tolbutamide.
It was assumed that the preprandial administration of glibenclamide was effective for the treatment of diabetes mellitus.

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Many investigators have postulated that dopamine plays a role in the regulation of secretions of some pituitary hormones. L-DOPA crosses the blood brain barrier and is decarboxylated in brain cells to dopamine. Acute effect of L-DOPA, however, failed to show detectable changes in plasma TSH level and thyroid function in human subjects. An attempt was made to determine the effect of L-DOPA on hypothalamic-pituitarythyroid axis in the rats.
The rats were fed a Purina laboratory chow (Purina) or Remington type low-iodine diet (LID) plus propylthiouracil (PTU). The 4 hr thyroid ¹³¹I uptake and serum T₄ concentrations were lower in L-DOPA (10 and 50 mg daily, for 3 days) treated groups than in the controls after PTU withdrawal. The relative composition of iodothyronines in the digested thyroids of rats was lower than that in the controls only when the higher concentration of L-DOPA was used. No thyroid enlargement after L-DOPA administration was found. No effect of L-DOPA on tissue uptake of labeled thyroxine in the presence of plasma was observed. In addition, no change in thyroid function was seen after a single injection of L-DOPA in PTU withdrawal rats or administration of L-DOPA to rats fed Purina. Nevertheless, a marked elevation in plasma TSH concentration after 10 mg or 50 mg of L-DOPA treatment was found in both Purina-fed and LID-fed rats. Similar observations were also obtained with dopamine.
Thus it seems unlikely that L-DOPA could be regarded as a simple goitrogen. The increase in plasma TSH concentration produced by L-DOPA in such animals is presumably due to direct stimulation of dopamine on TSH secretion mechanism. Since Rapoport et al. have recently observed suppressive effect of L-DOPA on serum TSH in hypothyroid patients, the present study suggests first a species difference in TSH response to L-DOPA.

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Purification and Biochemical character of hPL were already described (Folia Endocri. Japon., 49,882 and 49, 1059, 1973).
In this paper, the author describes the immunological character of hPL and the method of the immunological measurement using its antigenecity. Anti-hPL serum was prepared by injecting purified hPL-Kobe with complete Freund's adjuvant into the male guinea pig or male rabbit, and had the specific titer to show cross reaction with 25 μg/ml hPL on Ouchterlony, but no cross reaction with human serum.
1. Immunological Character of HPL-Kobe
As reported, the biological action of hPL includes somatotropic or metabolic action (Sciarra et al., 1963, Tojo et al., 1972, Tanaka, 1972) and lactogenic or luteotrophic action (Ito & Higashi, 1961, Josimovich et al., 1962). So the cross-reactivity of antihPL serum was investigated on Ouchterlony immunodiffusion against the human pituitary proteohormones, such as human growth hormone (hGH) and human prolactin (hPRL), or the human chorionic such as human chorionic gonadotropin (hCG) and human chronic thyrotropin (hCT).
HPRL, hCG and hCT did not show the precipitation line against anti-hPL serum and a single line was observed against hGH which showed only a partial identity for hPL. On immunoelectrophoresis using anti-hGH serum, hGH and hPL showed a single precipitation line in agar gel and hGH migrate more rapidly to the cathode. These results reveal that hPL shares antigenic determinants not present in the other.
2. Immunoassay o f HPL
For the estimation of human placental lactogen (hPL) three different immunoassay procedures, such as radioimmunoassay (RIA), single radial immunodiffusion (SRI) and hemagglutination inhibition reaction (HAIR) are reported here.
(1) HPL-Double Antibody Radioimmunoassay (HPL-RIA)
HPL-Kobe was used as the standard sample or the sample for iodination, and antisera to hPL was prepared in guinea pig against a purified hPL-Kobe. The iodination step presently used followed after the procedure described for growth hormone (Greenwood et al., 1963) with very minor modification. The reaction time of chloramin T was 15 sec.. The dilution of anti-hPL serum was 1 : 10000, first incubation time was 48 hrs.. and second incubation time was 24 hrs.. The standard curve obtained was sensitive, and unlabelled hPL over 0.006 μg/ml was measurable. Using this method, serum hPL of the normal pregnant woman was measured, which revealed that hPL was detectable on the 8th week of gestation. The concentration was 0.03-0.01/μg/ml. Thereafter, it rapidly increased to reach a peak of 4-10, μg/ml at term. A small amount of hPL was detectable in the cord blood and urine of the pregnant woman. Serum hPL was very low or undetectable in the abnormal pregnancy with hypofunction or dysfunction of placenta such as threatened abortion which terminated in abortion, ectopic pregnancy, fetal death in utero and hydatidiform mole. These facts indicate that measurement of serum hPL in the pregnant woman by hPL-RIA is one of the helpful ways to judge pla-cental function.
(2) HPL-Single Radial Immunodiffusion (HPL-SRI)
The principle of SRI reported by Mancini et al. (1965) was applied to the measurement of hPL. The conditions of method were determined by easiness to read the precipitation ring and the area of the ring : anti-serum concentration in the agar plate, 1.0% : thickness of the plate, 1.2 mm. : the diameter of the well, 4 mm. HPL-Kobe as a standard sample was diluted at stepwise concentration and placed in the well. Three days later, the diameter of each precipitation ring formed a line with 5.48 of regression coefficient and the sensitivity was 5μg/ml. When serum hPL of normal pregnant women was measured simultaneously by hPL-SRI and hPL-RIA, the values measured by hPL SRI were 2-3 times higher than those by hPL-RIA. But normal ranges by both methods increased with identical pattern.

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It was reported that there was a relationship between the acetate metabolism and TCA cycle in rumen epithelium of sheep. The present study was designated to elucidate how this relationship was influenced by starvation and alloxan treatment.
The results obtained are summarized as follows. There was no effect of the addition of citrate or succinate on the ¹⁴C transfer from ¹⁴C-acetate into CO₂ glucose, ketone bodies and lipid fractions and there was also no effect of the acetate addition on the ¹⁴C transfer from ¹⁴C-citrate or -succinate into all these fractions in rumen epithelium of normally fed sheep. In rumen epithelium of starved sheep, the ¹⁴C transfer from ¹⁴C-acetate into ketone bodies, cholesterol, NEFA and phospholipid was increased and the ¹⁴-glucose formation from C-acetate was decreased by the addition of citrate, and the ¹⁴-transfer from ¹⁴-citrate into ketone bodies, triglyceride and phospholipid was decreased by the addition of acetate. But in rumen epithelium of alloxan diabetic sheep, there was no effect of the citrate addition on the acetate metabolism, and there was also no effect of the acetate addition on the citrate metabolism. In rumen epithelium of starved and alloxan diabetic sheep, the ¹⁴ transfer from ¹⁴-acetate into ketone bodies, cholesterol, NEFA and phospholipid was increased by the addition of succinate, and the ¹⁴C transfer from ¹⁴-succinate into ketone bodies, cholesterol and phospholipid was increased by the addition of acetate.
As mentioned above, the relationship between acetate metabolism and TCA cycle in rumen epithelium of sheep was changed by starvation and alloxan treatment.

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It was reported that there was a relationship between the propionate metabolism and TCA cycle, and that starvation and alloxan treatment influenced the propionate metabolism, and the relationships between the propionate metabolism and glucolysis were changed by the alloxan treatment in the rumen epithelium of sheep. Further study was designed to elucidiate the relationship between the propionate metabolism and TCA cycle, and how this relationship was influenced by the starvation and alloxan treatments. The following results were obtained in a study on influence of citrate or succinate on the ¹⁴C-propionate metabolism and of propionate on the metabolism of ¹⁴C-citrate or -succinate in the rumen epithelium of normally fed, starved and alloxan diabetic sheep.
In the rumen epithelium of normally fed and starved sheep, the ¹⁴CO₂ formation from ¹⁴C-propionate was increased and the transfer of ¹⁴C from ¹⁴C-propionate into glucose, triglyceride and phospholipid was decreased by the addition of citrate or succinate. And also the formation of ¹⁴CO₂, ¹⁴C-triglyceride and-phospholipid from ¹⁴C-citrate or-succinate was increased and the transfer of ¹⁴C from ¹⁴C-citrate or-succinate into glucose, ketone bodies and cholesterol was decreased by the propionate addition in the rumen epithelium of normally fed and starved animals.
Furthermore, the citrate effects on the propionate metabolism and the propionate effects on the citrate metabolism were disappeared by the alloxan treatment. But the succinate effects on the propionate metabolism and the propionate effects on the succinate metabolism were observed in the rumen epithelium of alloxan diabetic animals.
As mentioned above, the citrate or succinate showed the various effects on the propionate metabolism and also the propionate had various effects on the metabolism of citrate and succinate, and these relationships between the propionate metabolism and the citrate metabolism were changed by alloxan treatment in the rumen epithelium of sheep.

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