The important role of renal gluconeogenesis in blood glucose homeostasis has been widely accepted. In order to clarify the details of this phenomenon, gluconeogenesis from various substrates in the kidney from starved and/or partially hepatectomized rats was studied using perfusion techniques.
Gluconeogenesis from oxaloacetate, 2-oxoglutarate, glutamate and glutamine was stimulated significantly by 24h fasting whereas, glucose production from pyruvate and lactate was not enhanced by fasting. With a combination of 24h fasting and partial hepatectomy, gluose production from the latter two substrates showed a tendency to increase. Glucose formation from fructose was stimulated significantly by 24h fasting, but there was no additive enhancement with combined partial hepatectomy.
These data suggest that, (1) the gluconeogenic process from fructose was stimulated by 24h fasting, but that partial hepatectomy combined with fasting was not effective, and that (2) the gluconeogenic process after oxaloacetate was enhanced by 24h fasting, while the process after pyruvate and lactate was stimulated by the addition of partal hepatectomy to fasting. In other words, phosphoenolpyruvate carboxykinase (PEPCK) in kidney was induced by 24h fasting or by partial hapatectomy, and pyruvate carboxylase was induced by the combination of 24h fasting and partial hepatectomy.
In fact, a significant increase in renal PEPCK activity after 24h fasting, and an additive effect of partial hepatectomy to enzyme activity, were demonstrated. The changes in the levels of corticosterone and glucagon in plasma did not correlate with the magnitude of gluconeogenesis or PEPCK activity. Metabolic acidosis was observed neither in fasting nor in partially hepatectomized rats.
The possible role of the reduction of plasma insulin levels and/or blood glucose as a trigger of the above-mentioned metabolic changes might be considered.

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The present study was undertaken to elucidate the abnormality of vitamin E metabolism in diabetes. Four different groups of eight rats each were studied. The control group consisted of normal rats, and the second group of untreated diabetic rats induced by administration of streptozotocin. The third group was made up of diabetic rats treated with lente-MC insulin, and the fourth group was treated with vitamin E. Each animal was observed for a period of four weeks. The vitamin E levels of plasma and high-density lipoprotein (HDL) fraction were measured by the method of Abe and Katsui. The vitain E levels of several organs (liver, kidney, and pancreas) were measured by high-performance liquid chromatography.
The percentage of vitamin E in HDL to plasma in diabetic rats was 21.4±3.0%(Mean±SD), which was significantly lower than that in control rats (31.5±10.3%)(p<0.05). When diabetic rats were treated with insulin, this abnormality of vitamin E percentage in diabetic rats was significantly improved to the level of control rats. These findings suggested that the abnormality of vitamin E metabolism in diabetic rats could be due to the deficiency of insulin, and that insulin treatment could be effective for this abnormality in diabetes. In diabetic rats treated with vitamin E, the low level of percentage vitamin E of HDL to plasma was also significantly improved. This finding suggested that vitamin E treatment might be effective for the abnormality of vitamin E metabolism in diabetes without insulin treatment, and that there may be another mechanism of this abnormality in diabetes.
The vitamin E content of liver in diabetic rats was 24.5±5.7μg/g.w.w., which was significantly lower than the value of 35.4±9.9μg/g.w.w. in control rats (p<0.05). When diabetic rats were treated with insulin or vitamin E, this abnormality was improved.

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The platelet activating factor (PAF), a platelet aggregation inducer, is considered to activate platelets not through the mediation of ADP or thromboxane, but by a new pathway. The author tested the platelet aggregation using PAF and otherinducers in 50 healthy individuals and 73 diabetic patients, and compared the test results. Diabetic patients were divided into 2 groups, one with 51 patients exhibiting no variation in blood glucose level for 6 months (stabilized blood glucose group) and the other with 22 patients from whom blood was collected around 2 weeks after the initiation of blood sugar control (reduced blood glucose group). Aggregation inducers used were 0.5μg/ml PAF, 3μM ADP. 10μg/ml collagen and 9.3μg/ml epinephrine.
In healthy individuals, PAF-induced aggregation was 56.4±11.8%. Though there was no significant difference between sexes or among age groups, PAF-induced aggregation tended to be higher for people in their 20s or 30s than for those in their 60s. A positive correlation existed between PAF-induced aggregation and ADP-induced aggregation or collagen-induced aggregation.
In diabetic patients, PAF-induced aggregation was 37.8±26.1%, significantly lowered as compared with that in healthy individuals. A positive correlation existed between PAF-induced aggregation and ADP-induced aggregation or collagen-induced aggregation, or epinephrine-induced aggregation. Between the stabilized blood glucose group and reduced blood glucose group, a significant difference was detected in PAF-induced aggregation at the 0.1% significance level, with on aggregation rate of 30.1±22.1% for the former and 55.8±26.3% for the latter. In the stabilized blood glucose group, no significant difference was detected between patients with good blood glucose level and those with high blood glucose level.In the reduced blood glucose group, PAF-induced aggregation was positively correlated with platelet count, and negatively correlated with blood viscosity.
PAF-induced aggregation was closely correlated with the aggregation induced by other substances. However, in diabetic patients, PAF-induced aggregation alone was significantly lowered as compared with that in healthy individuals, and it was significantly heightened in patients examined around 2 weeks after the initiation of blood sugar control as compared with that in patients with blood glucose stabilized for over 6 months.

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In order to clarify the relationship between radiographic changes in the pancreatic duct by ERCP and pancreatic endocrine function, the 100g oral glucose tolerance test (GTT) and arginine tolerance test (ATT) for the evaluation of pancreatic endocrine function were performed in 65 patients with chronic pancreatitis, and in five control subjects with normal pancreatogram and glucose tolerance. The patients with chronic pancreatitis were divided into three groups according to ERCP findings (advanced pancreatitis: ADP, n=7, moderate pancreatitis: MOP, n=35, minimal pancreatitis: MIP, n=23).
The sum of glucose levels at basal, 30, 60, 90, and 120 min during 100g OGTT in the ADP group was significantly higher than that in the MOP and MIP groups or controls. The ratio of increments of plasma insulin (IRI) above basal level at 30 min to that of glucose (insulinogenic index) during GTT was significantly lower in each type of chronic pancreatitis tham in controls. On the other hand the ratio of the sum of IRI increments above basal level at 30, 60, 90 and 120 min to that of glucose (ΣΔIRI/ΣΔBS) during GTT in each type of chronic pnancreatitis was not significantly different from controls. However, both indices in each subgroup consisting of patients with diabetic gluose tolerance were significantly lower than in controls. There were no significant differences in the sum of increments of both IRI (ΣΔIRI) and glucagon (ΣΔIRG) for 2 hours during ATT in the MIP, MOP or ADP group in comparison with controls. However, ΣΔ IRG during ATT in the ADP group was significantly lower than that in the MOP group. These results suggest that glucose intolerance in ADP is associated with decreased insulin secretion, and that pancreatographic changes in MIP or MOP are not correlated with pancreatic endocrine function.

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In 38 cases of esophageal cancer with glucose intolerance, we studied the administration of insulin during and after surgery and whether glucose-containing fluids should be infused from the beginning of surgery. On the operation day, conventional insulin injection or oral hypoglycemic agents were omitted, and the blood glucose levels were measured every 30-60 minutes during surgery, continuous intravenous insulin infusion (CIVII) being started when the blood glucose level exceeded 200 mg/dl. CIVII was carried out during surgery in all of the cases given glucose infusion from the beginning of surgery (G (+) group), and in 70% of the cases without glucose infusion at the beginning of surgery (G (-) group). As a rule, CIVII was changed to continuous subcutaneous insulin infusion (CSII) on the second day after the operation.
The results obtained were as follows:
(1) In the G (+) group, the effect of insulin in the early postoperative period was significantly higher than that in the G (-) group. There was no statistically significant difference between the two groups in plasma free insulin, free fatty acid, lactate and urea-N. However, the levels of plasma freee fatty acid and lactate were remarkably elevated during surgery in the G (-) group, indicating that metabolic abnormality was greater in the G (-) group. Therefore, in cases requiring long-duration surgery, such as that for esophageal cancer, it is necessary to administer glucosecontaining fluids and to control blood glucose with insulin from the beginning of surgery.
(2) Insulin treatment by CSII following CIVII was a simple, safe and effective way to control blood glucose in postoperative cases receiving intravenous hyperalimentation, in which glucose administration was increased stepwise.
(3) The amount of glucose infused was about 350 g per day after the third postoperative day, and blood glucose was controlled by CSII at a rate of less than 2 units per hour. Even in cases with mild glucose intolerance, 0. 5-4 unit per hour was required to control blood glucose.

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Periodontal disease including gingivitis and periodontitis were examined in 147 diabetic patients and 75 non-diabetic subjects. Periodontal disease was assessed by the evaluation of 4 oral cavity examinations: Bleeding Index (BI), Periotron Value (PT), Pocket Depth (PD) and Plaque Control Record (PCR).
Diabetic patients had lost more of their teeth than non-diabetic subjects (p<0.01). Also BI, PT and PD in diabetic patients were significantly elevated compared to those in age-and PCRmatched non-diabetics (p<0.05, p<0.01, p<0.01), respectively. In poorly controlled diabetics, BI and PT were evidently elevated in comparison with those in well cotrolled diabetics. Progression of periodontal disease may tend to occur in patients with microangiopathy, such as retinopathy, and with a relatively prolonged duration of diabetes.
Worsening of periodontal disease in diabetic patients could be prevented by both oral cleaning and good metabolic control of diabetes, particularly diabetic blood glucose control.

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Pancreatic exocrine acinar cells in NOD mice, an animal model of Type 1 diabetes, were examined in relation to the numbers of zymogen granules and the incorporation of leucine-³H.
(1) There were no differences between the acinar cells in NOD mice aged three weeks and those in age-matched ICR mice with regard to the numbers of zymogen granules and the incorporation of leucine-³H.
(2) Acinar cells in NOD mice aged three to five months, which were accompanied by insulitis, showed the depletion of zymogen granules and incorporation of leucine-³H, mildly in the normoglycemic group and markedly in the hyperglycemic one, when compared with those in agematched ICR mice.
(3) The hyperglycemic NOD mice showed the marked depletion of acinar zymogen granules in the fed state, and, a prominent delay in the recovery of the zymogen granules after cerulein stimulation was undertaken.
(4) The decreased rate of protein synthesis in the exocrine acinar cells is thought to be one of the main causes of the decreased numbers of zymogen granules in NOD mice accompanied by insulitis.

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Our report concerns a housewife diagnosed as diabetic at 9 years of age. Through planned pregnancy, she bore a normal, healthy infant after having given birth to one suffering from multiple anomalies and osteogenesis imperfecta congenita, most probably due to the mother's poor diabetic control.
Insulin therapy was begun when the woman's diabetes was first diagnosed. Blood glucose control with 50 to 80 units of insulin was poor. At the age of 23, she came to the Diabetes Center in April 1981, in the 11th week of her first pregnancy. Her fasting blood glucose was 196mg/dl and HbA₁ was 11.6%. Despite 14 years of diabetes, she had diabetic retinopathy of Scott's Ia in her right eye only and no diabetic nephropathy. She was immediately admitted to the Center, and underwent strict diet therapy and insulin injections four times daily. Her blood glucose control improved to where it was almost satisfactory after she was discharged. A girl was born spontaneously in the 38th week of gestation, but the infant died within 30 minutes due to multiple anomalies, osteogenesis imperfecta, and nonspontaneous respiration.
After the first delivery, the woman normalized her blood glucose through home-monitoring, and conceived a second infant in a planned pregnancy. Her diabetic control was HbA₁ 8.4-9.4% and she had no diabetic microangiopathy. She gave birth spontaneously to a 2707g girl in the 37th week of gestation. The infant suffered no abnormalities or complications.
Again, this case demonstrates the importance of planned pregnancy in enabling even a diabetic diagnosed at the age of 9 to experience a normal pregnancy and bear a normal infant.

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A case of chlorpropamide-associated aplastic anemia is described. A 46-year-old diabetic man began to complain of breathlessness and easy fatiguability after administration of about 35g of chlorpropamide in February 1982. The peripheral blood cell count showed pancytopenia (Hb 6.6g/dl, WBC 2, 200/mm³, platelets 15, 000/mm³). Bone marrow aspiration revealed a hypoplastic marrow. Chlorpropamide was discontinued and subcutaneous insulin administration was started to control the high blood glucose. The patient was treated with Prednisolone for 7 weeks with satisfactory improvement in peripheral blood cell counts (Hb 10.2g/dl, WBC 5, 200/mm³, platelets 180, 000/mm³) as well as in the bone marrow. His clinical course suggested that the aplastic anemia was secondary to chlorpropamide administration.
So far 17 cases of hematological disorders associated with chlorpropamide have been reported. In most cases the illness developed when the total doses given amounted to nearly 10g. Only one case of aplastic anemia and two cases of bone marrow hypoplasia were included in these reports. Four patients with granulocytopenia died.
Peripheral blood cell counts should be performed to avoid side effects during chlorpropamide administration.

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We present a 46-year-old man who showed acutely progressive diabetic retinopathy and who was diagnosed as “severe retinopathy at an adjacent papilla”.
This nonobese patient with NIDDM, noticed thirstiness in 1982. He was indicated as having glucosuria and visited our clinic in March 1984.
His blood glucose level was 487 mg/dl, HbA₁ was 15.3%, and urinalysis revealed proteinuria. Fundus examination revealed Scott IIIb, and simple retinopathy was diagnosed. He was treated by diet and small-dosage insulin injections.
Three months later, in July 1984, fundus examination showed preproliferative retinopathy, and panretinal photocoagulation (PRP) was performed. Recognizing the presence of retinopathy, we controlled the patient's blood glucose level carefully to prevent a rapid lowering of the fasting blood glucose level.
However, soon after the PRP was completed, the patient's sight acuity diminished rapidly. Massive hemorrhages, exudates and lipid deposition on the posterior pole appeared. In September 1984, fluorescein angiography revealed neovascularization of the optic disc and the patient was diagnosed as proliferative retinopathy. In April 1985, vitreous hemorrhage occurred bilaterally. The fundus showed massive hemorrhages, exudates and lipid deposition throughout the posterior pole, and PRP was not effective. Hence, the condition was diagnosed as “severe retinopathy at an adjacent papilla”.
The onset was two years previously, so the duration was not long. The patient was not hypertensive or obese, Blood glucose was controlled carefully. The cause of deterioration in this case is uncertain, and no clear risk factor except for mild proteinuria can be found. There might be a relationship between the progress of retinopathy and nephropathy.

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This is the first reported case of the successful treatment of a patient with hyperosmolar nonketotic diabetic coma (HNKDC) complicated by rhabdomyolysis, disseminated intravascular coagulation (DIC), and renal and respiratory failure.
A 21-year-old man with a few weeks' history of polyuria and increasing thirst was admitted to hospital in comatose state (plasma glucose 998mg/dl, ketonuria ±). Although he had been treated with rehydration and small amounts of insulin, his consciousness did not improve, and oliguria occurred. For these reasons, he was transferred to our hospital. Physical examination revealed profound dehydration, shallow respiration, and comatose state. Investigations showed plasma glucose of 518mg/dl, serum osmolarity of 424mOsm/kg H₂O, serum Na 181mEq/l and creatinine of 3.0mg/dl. Ketonuria was absent. Arterial blood gases on air showed respiratory acidosis. The elevation of enzymes originating in muscle tissue (CPK, 16590 mU/ml, Isozyme MM, 99%) and scum myoglobin (250×10⁴ng/ml) were observed. In addition, hemostatic abnormalities were considered compatible with the DIC. Histological findings of muscle and renal biopsy also revealed changes consistent with rhabdomyolysis and acute tubular necrosis, respectively. Soon after admission, he was carefully rehydrated and the diabetes was brought under control with low-dose insulin infusions. Simultaneously, ventilatory support and continuous infusion of gebexate mesilete (FOY, 1000mg/day) were started. The dehydration, hyperglycemia and ventilatory failure responded satisfactorily to these therapies, but hemodialysis was started on the fourth day after admission because anuria developed. With these thrapeutic regimens his condition improved gradually, i. e., clinicl recovery was complete without significant consequences on the 50th day.

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The myo-inositol (MI) content of various nerve tissues obtained from streptozotocin (STZ)-diabetic rats was measured in order to clarify the role of abnormal MI metabolism in the development of diabetic neuropathy.
Diabetes was induced in Sprague-Dawley rats by intravenously injecting 50mg/kg STZ. One group of diabetic rats was used for the experiment 3 days after the STZ injection and other group 14 days later. Weight-matched rats were used as controls. Cerebral gray matter, dorsal root ganglia (DRG), and sciatic nerve were quickly removed from those rats after decapitaton. Further, nerve cell-rich parts (DRG cells) were excised from the DRG under microscope. These samples were homogenized in 1ml of distilled water and deproteinized by adding ZnSO₄ and Ba (OH) ₂. Free MI in the extracts was measured by highperformance thin-layer chromatography.
The MI content in the cerebral gray matter was the same in the three groups, but it was significantly decreased in the DRG cells of the 14-day diabetics. In the sciatic nerve the MI was significantly decreased in both the 3-day and 14-day diabetic rats compared with the controls. In the control group, the MI content was significantly different among the cerebral gray matter, DRG cells, and the sciatic nerve.
These results indicate that the abnormal MI metabolism appears first in the distal portion of the peripheral nervous system in diabetic rats. This differnce in MI metabolism between central and peripheral nerve tissues may explain the predominant occurrence of peripheral neuropathy in diabetes mellitus.

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