Hyperglucagonemia has been reported in patients with liver disease. However, the etiology of the high plasma glucagon level in liver injury remains unclear. An attempt was made to determine whether this hyperglucagonemia is a consequence of hypersecretion or not. Dogs with acute liver damage induced by carbon tetrachloride were used. Levels of immunoreactive glucagon (IRG) which reacts with antiserum 30 K and immunoreactive insulin (IRI), were determined. Blood samples were obtained from the pancreatic vein and femoral artery after L-arginine infusion and I.V. glucose. The results obtained were as follows.
1) The blood glucose levels after arginine infusion were low in the hepatic injury group compared to those of the control group.
2) The arterial IRG and pancreatic venous IRG levels after arginine infusion were significantly higher in the hepatic injury group compared to those of the control group.
3) IRG secretion as calculated using these pancreatic venous and arterial IRG values and the pancreatic plasma flow, was hyperresponsive in the hepatic injury group throughout the arginine infusion.
4) The levels of arterial and pancreatic venous IRI after arginine infusion in the hepatic injury group were the same as those of the control group.
5) The IRG suppression rate after I.V. glucose in the hepatic injury group was the same in the early phase of the study as in the control group.
6) Histological findings for the pancreas in the hepatic injury group revealed no particular changes in the islets of Langerhans' as compared to the control group.
Based on these data, it is concluded that in dogs with acute liver damage induced by carbon tetrachloride, hyperglucagonemia is a consequence of hypersecretion of pancreatic A cells. Also, in dogs with acute liver damage, suppression of IRG by glucose was noted.

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Using a sensitive anti-somatostatin serum acquired by the method of Arimura, the validity of somatostatin-like immunoreactivity (SLI) measurements in urine was examined by radioimmunoassay (RIA). The antisomatostatin serum, No.S 307, was specific for somatostatin, and its final concentration used in the RIA was 1: 45, 000. The radioimmunoassay employed had a sensitivity of 2 pg/ ml. The coefficient of variation for intra-and inter-assays was 8% and 19%, respectively. The recovery of synthetic somatostatin added to the urine was 96.7%. Serial dilutions of urine samples with added synthetic somatostatin gave proportional readings. Based on these results, it is considered that there may be no radio-immunoassay inhibitors in urine. As the SLI in urine was relatively stable, it seems to be suitable for measurement. Urine SLI was eluted by gel filtration on Sephadex G 25 as a single peak in the region corresponding to synthetic somatostatin, suggesting that the two have similar molecular weights.
An additional study, using canine urine, revealed that following somatostatin infusion, urine SLI levels rose. This indicates that urine SLI levels tend to reflect the SLI levels in plasma. The measurement of SLI in urine in this study may thus represent one of the useful methods for determining the pathological and physiological role of circulating somatostatin. Studies on diurnal changes in urine SLI in normal subjects were also performed. The mean basal level of urineSLI in normal subjects was 167±45 pg/hr (mean±S.E.M.), and rose significantly after lunch and supper (p<0.01).
It is considered that ingested nutrients cause SLI release from the stomach, intestine and pancreas into the venous effluents, directly or via gut hormones, leading to a rise in urine SLI level.

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The clinical course and pancreatic B-cell function of diabetics (males 7, females 3) newly diagnosed after the age of 25 years, were studied. Fifty g oral glucose tolerance tests (50 g OGTT) were performed before and after treatment, and the IRI (CPR) respons was measured at the same time.
Immediately after admission, intensive insulin therapy was begun and remission was obtained in 5 out of the 10 patients (males 3, females 2). The other 5 patients (males 4, female 1) wre continued on insulin therapy.
The patients who experienced remission had been overweight (24±2.3% of ideal body weight) before the onset of diabetes.
The fasting blood glucose (FBG) level on admission was 321±57 mg/dl and the IRI response to 50 g OGTT showed a low and flat pattern. Insulin therapy was discontinued when the FBG level fell 74±3 mg/dl. The maximum dosage for the insulin therapy was 28.8±6.4 U/day. At this point, bodyweight was normal (8.8±2%) and a marked elevation of the CPR response to 50 g OGTT was observed.
Two out of the 5 remission cases showed overt diabetes with insulin therapy over periods of 3 months and 1 year and 3 months, respectively. At this point, their CPR response to 50 g OGTT dropped to a low and flat pattern again.
The clinical pictures of the 5 patients without remission were similar to those of cases with remission except that the patients were not obese (10.2±3%) before the onset of diabetes and recovery of endogenous insulin response was not observed.

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The correlation between HbAic and microangiopathy and other parameters was studied in 161 diabetic patients under continuous diabetic therapy over a period of 3 months.
The results obtained were as follows.
1) The HbAic concentrations in the 161 diabetics correlated with the fasting blood sugar (FBS) measured with the same samples, and with the mean FBS levels over the past 3 months (γ=0.55, p<0.001).
2) Even in groups with FBS below 119 mg/dl, the HbAic concentrations were higher than in normal subjects (6.69±1.88% and 5.33±0.63%, respectively; p< 0.02).
3) The HbAic levels were high in patients treated with diet alone, sulfonylurea and insulin, in that order.
4) The concentrations of HbAic did not correlate with sex, age, duration of diabetes, serum triglyceride or total cholesterol.
5) In groups with FBS below 140 mg/dl, the HbAic levels were higher in diabetics with albuminuria than in those without albuminuria (p <0.05).
6) Higher HbAic levels were found in patients with proliferative retinopathy (7.11±0.8%) than in those with background retinopathy (6.15±1.1%) or with no retinopathy (6.24±0.6%, p<0.02).
These results suggest that HbAic may be related to the development of diabetic microangiopathy.

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Autopsy pancreases from diabetic and nondiabetic individuals were subjected to quantitative morphological analysis of their islets, and the results were compared with data for glucose tolerance examined during life. Islets were regarded as spheres of different radius r, and the Weibull function was assumed to represent the basic distribution curve for r. The stereological theorem derived by Suwa and us was employed to estimate the total islet number N_i and the total volume V_i is the organ, the mean islet radiusand the mean volume V_i of a single islet. Morphometry was based on chord length measurements for a sufficient number of islets in histological sections.
The materials consisted of pancreases from 26 maturity-onset and 5 juvenile-onset diabetics and 28 nondiabetics. In addition, 9 hypertensives without diabetes were included in order to evaluate the injurious effects of multiple lesions of pancreatic arterioles. V_i was 0.97, 0.60 and 0.26 cm³ in the control, maturity-onset and juvenile-onset diabetic groups, respectively. Any two of the values were statistically significant. In the hypertensive group, V_i was 0.84 cm3, which was not significantly lower than the control level. Correlation analysis of V_i revealed a definite negative relationship with BS_man the maximum blood sugar level during 50 g oral GTT. This relation was consistent not only for the pool of all the cases examined, but for either the diabetic or nondiabetic group alone. A similar negative correlation was noted in the diabetics between V_i and FBS, the level ol fasting blood sugar. These results confirmed the functional importance of V_i as a morphological measure of glucose tolerance.
As for N_i, r, and V_i, no significant difference was demonstrated between the diabetic and control groups. Although there was an obvious negative correlation between N_i and r, both the diabetic and nondiabetic subjects showed uniform distribution on N_i-r coordinates, failing to characterize the diabetic pancreas in this aspect.

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In our foregoing report, it was shown that the total islet volume Vi of the pancreas represents the sole morphological index of glucose tolerance and intolerance. As a further extension of that study, we examined the relative volumes of A, B and D cells in diabetes histometrically, and correlated them with clinical data. Autopsy pancreases from 26 maturity-onset and 5 juvenile-onset diabetics and 18 nondiabetics were subjected to volumetry. For differential staining of specific granules, paraffin sections from each pancreas were treated by Gomori's aldehyde fuchsin trichrome method. The volume ratio between the different islet cells in the sections was determined by the point counting method using a square-lattice eye-piece.
The results obtained may be summarized as follows.
1) The volume ratio between A, B and D cells was almost the same in the diabetic groups as in the controls. Especially noteworthy was the fact that the percentile volume of B cells was constantly about 65% in all three groups.
2) The absolute total volume V_B of B cells in the pancreas was 0.64 cm³ in the control, but only 0.39 and 0.16 cm³ in the maturity-onset and juvenile-onset diabetic groups, respectively. The total volume of A cells was also reduced in the diabetic groups.
3) BS_max, the maximum blood sugar level during oral GTT, increased with decreasing total B cell volume V_B. There were some nondiabetics with smaller V_B and concomitantlysomewhat higher BS_max, and these overlapped with diabetics in the range of V_B from 0.4 to 0.6 cm³. It seems quite likely that such cases represented potential diabetics (socalled prediabetics), and may be defined as such by the transitional nature of not only their clinical but also their morphological features.
4) In the diabetic group, the smaller the value of V_B, the higher was the level of fasting blood sugar.
5) V_B diminished with descending age at onset of diabetes.
All the above findings areconsidered to support the primacy of insulin deficiency in the pat hophysiology of diabetes.

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The contaminating Proinsulin-Like Immunoreactivity (PLI) of several insulin preparations recently on the market was determined directly and after gel filtration by porcine and bovine proinsulin-specific radioimmunoassay.
Although gel filtration of 800 μg of Novo lente gelchromatographed insulin revealed neither porcine nor bovine Proinsulin-Like Components (PLC), apparent porcine and bovinePLC were detected after gel filtration of 800 μg of single peak insulin (lente insulin “Lilly” U-40, lente insulir “Lilly” U-100, regular insulin Iletin U-100) and 100 μg of Novo regular insulin by the specificradioimmunoassay.
The gelchromatographed insulin preparation contained less than 0.00045% of porcine and bovint PLI, but the regular insulin preparation from the same company contained 0.93 % of porcine and bovine PLI by weight as estimated directly with the specific-radioimmunoassay methods foi porcine and bovine PLI.
Single peak insulin preparations contained about 0.2 to 0.6% of porcine or bovine PLI by weight as estimated directly.

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