A method for quantitative measurement of IgG in rat urine was developed using enzyme immunoassay (sandwich method) and applied to the study of diabetic rats. IgG concentration in rat urine could be measured within the 10-1, 000 ng/ml range. This method made it possible to measure many samples at one time as a result of easy procedures using simple equipment. In non-treated male wistar rats (BW 200 g, n =7) urinary IgG was 120+53 pg/day. On the 10th day after intravenous administration of streptozotocin (55 mg/kg BW), urinary IgG increased to 349 ± 46 pg/day, which was signficantly different from levels in the controls (p<0.01). These results showed that urinary IgG increased beginning with the initial stage of onset of diabetes. Measurement of urinary IgG, which serves as an index of early renal damage in diabetes mellitus, will be useful in understanding the pathophysiology of renal damage. Variations of assay were satisfactory: 9.0-13.1% “intra-assay”, 6.1-14.3% “inter-assay” and 91-107%(mean: 97.5%) “recovery test”.

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A teratogenic property of mannose has been reported in animal studies. To elucidate the clinical significance of mannose in pregnancy we measured fasting serum mannose in sixtyeight pregnant diabetics in the first, the second and the third trimester using a gaschromatograph.
In 120 normal pregnancies the fasting serum mannose levels were 0.64±0.28 mg/dl in the first trimester, and there was no significant change during the remainder of pregnancy.
In the pregnant diabetics the fasting serum mannose levels were 0.84±0.45 mg/dl in the first, 0.75±0.41 mg/d/ in the second and 0.69±0.36 mg/d/ in the third trimester. These levels were higher than those in healthy pregnant women.
There was a significant positive correlation between fasting serum mannose and glucose levels. Three out of ten women whose mannose levels were high in the first trimester had spontaneous abortions, however, we were unable to find any direct evidence of an effect of hypermannosemia on malformation of infants of diabetic mothers, because none of the infants born of the diabetic mothers examined had malformations.

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[in Japanese]

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The effects of maternal hypoglycemia during early pregnancy on skeletal development in offspring from normal (n=19) and subdiabetic rats (n=18) were studied. Female Wistar rats were intravenously injected with streptozotocin (STZ, 30 mg/kg) or its vehicle 2 to 3 weeks before mating. Mild glucose intolerance was shown in STZ-treated rats by ip glucose tolerance test. On day 10.5 post-conception the dams received saline or Actrapid insulin (400 mU/rat) intraperitoneally. Hypoglycemia (around 50 mg/dl) was maintained for about 70 min in the insulin-treated dams. Pregnancy was terminated on gestational day 20. Fetal bone and cartilage were double-stained with alizarin red S and alcian blue 8GS. Delayed ossification and marked resorption were observed in offspring whose mothers had received insulin. Malformations of the sternum, ribs and costal cartilages were greatly increased. The influence of maternal hypoglycemia on skeletal malformation was greater in fetuses from diabetic dams than in those from control dams. These data suggest that maternal hypoglycemia in early pregnancy has a critical effect on skeletal development and malformation in rat fetuses. In addition, mild maternal glucose intolerance may amplify the teratogenic effects of hypoglycemia.

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During the initial stages of insect flight, adipokinetic hormone (AKH) is released from secretory cells in the corpora cardiaca and causes the release of specific diglycerides, which are used by the flight muscles as a source of energy. Recently, AKH has been demonstrated by immunohistochemical technique to be present in rat pancreatic tissue. In the present study, using a rat pancreatic perfusion system, the possible involvement of AKH in endocrine pancreatic function was assessed. In basal conditions, 10nM AKH induced about a 50% decrease in glucagon levels although there was no apparent effect on insulin secretion. Using 10mM arginine HCl and 18.5mM tolbutamide as secretagogues, the modulatory effects of AKH on insulin and glucagon secretion were examined. Arginine-induced insulin and glucagon secretion was significantly suppressed by the simultaneous administration of 1nM (p<0.05) or 10nM (p<0.05) AKH, while the tolbutamide-induced insulin secretion was significantly suppressed (p<0.05) without any significant change in glucagon secretion. These results indicate that a modulatory effect of AKH may exist in the endocrine pancreas and suggest that AKH may have some physiological role in the mammalian pancreas.

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A 28-year-old woman delivered an infant in another hospital. Her previous health had been excellent. There was no history of obesity nor family history of diabetes mellitus.
The patient was well until the 36th week of gestation, when anorexia, thirstiness, polyuria and body weight loss occurred and further developed. She did not take any medication for diabetes mellitus, and was able to deliver a 2, 310 g premature infant in the 38th week of gestation.
The infant had no complication or malformation. At four days after delivery, the mother lost consciousness and was transferred to our hospital. Her general condition improved with insulin therapy, however, low C-peptide levels in both plasma and urine did not recover, and she was diagnosed as having insulin-dependent diabetes mellitus (IDDM). Laboratory determination of HLA type revealed DR4.
Tests for islet-cell antibodies (ICA), anti-insulin antibodies, and various anti-virus antibodies were negative. Although the incidence of IDDM during pregnancy is rare in Japan, increased incidence of IDDM in the third trimester of gestation has been reported in Scandinavian subjects. The case is noteworthy in view of study of pathogenetic mechanisms underlying IDDM.

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A rare disorder of sigmoid paracolic abscess due to methicillin resistant staphylococcus aureus (MRSA) in a diabetic patient is described. A 44-year-old man with diabetes mellitus, hyperlipidemia and hypertension of 14-year duration had attended our hospital. He had no diabetic complications but had not followed basic diabetes treatament (diet and exercise). We repeatedly admitted our hospital to correct over weight gain and hyperglycemia. In February, 1989 he was again admitted to our hospital for treatment of fever, lower abdominal pain, diarrhea and anorexia. Physical examination revealed the presence of generalized muscular spasticity of the abdomen where a mass was palpable. The white blood cell count was 15900. Testing for C-reactive protein was positive (6 +). Fasting blood glucose level was 161 mg/dl andglycosylated hemoglobin A1 Content was 7.5%. The patient was immediately diagnosed as having panperitonitis and underwent laparotomy. In the sigmoid colon was found with a nodular mass containing on abscess. A specimen of the abscess yielded MRSA on culture. Barium-enema examination revealed some diverticular shadows in the sigmoid colon. We discuss the association of sigmoid paracolic abscess due to MRSA and diabetes mellitus and consider that good control of diabetes mellitus, including weight control, is important.

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Accumulation of sorbitol has previously been reported in rat mesangial cells cultured under high glucose conditions and has been linked to the impaired function of these cells in streptozotocin-induced diabetic rats. The presence of aldose reductase (AR, EC 1.1.1.21), a key enzyme in the sorbitol pathway, has also been reported in mesangial cells. The role of aldehyde reductase (ALR, EC 1.1.1.2), however, another enzyme catalyzing the conversion of glucose to sorbitol, has yet clarified to be in mesangial cells.
In the present study, an aldose reductase inhibitor, FK-366, was capable of significantly inhibiting DL-glyceraldehyde (GAD)-reducing activity in a concentration of 10^-8 M, but was unable to inhibit D-glucuronate (GLN)-reducing activity in cultured rat mesangial cells, even at 10-5M confirming the highly specific inhibitory activity of this compound on AR and suggesting simultaneous presence of both enzymes, AR and ALR.
FK-366 also significantly prevented the accumulation of sorbitol in mesangial cells cultured under high glucose (55 mM) conditions 10^-7M, the concentration at which the compound inhibited GAD-reducing activity but not GLN-reducing activity.
These results suggest that AR may play a major role in sorbitol accumulation in cultured rat mesangial cells under high glucose conditions, although sorbitol may be produced by other enzymes.

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