We have carried out the mass survey for diabetes mellitus by a 50 g GTT as the first screening since 1971. Average incidences of diabetic pattern, IGT pattern, borderline pattern and normal pattern in a Glucose Tolerance Test (GTT) were 2.3±1.8%, 6.6±1.7%, 19.8±6.6% and 71.4 ±7.8%, respectively. 21 males and 6 females were found to be diabetic by this survey for 11 years. Insulinogenic indices (I. Is.) of diabetic, IGT, borderline and normal patterns were 0.13±0.07, 0.70±0.37, 0.58±0.40 and 1.05±0.30, respectively, and the values of I. I. in diabetics and borderline diabetics were significantly lower than that in the normal pattern. A I. I. in the subjects who have revealed the normal glucose tolerance every year for 11 year, 2.62±1.28, was high in the normal range. On the other hand, a I. I. in the subjects who became overtly diabetic from the IGT, borderline or normal pattern, 0.36±0.31, was significantly lower. Therefore, taking into consideration that one of the characteristics of NIDDM is low insulin response to glucose, the mass survey for diabetes mellitus should be carried out by a Glucose Tolerance Test (GTT) as the first screening with the measurement of plasma insulin concentrations. A follow-up study for the low insulin responder is considered to be one of the most preferable investigations for the detection of the early stage of diabetes mellitus.

BACKGROUND: Damaged mitochondria are removed by autophagy. Therefore, impairment of autophagy induces the accumulation of damaged mitochondria and mitochondrial dysfunction in most mammalian cells. Here, we investigated mitochondrial function and the expression of mitochondrial complexes in autophagy-related 7 (Atg7)-deficient beta-cells. METHODS: To evaluate the effect of autophagy deficiency on mitochondrial function in pancreatic beta-cells, we isolated islets from Atg7(F/F):RIP-Cre+ mice and wild-type littermates. Oxygen consumption rate and intracellular adenosine 5'-triphosphate (ATP) content were measured. The expression of mitochondrial complex genes in Atg7-deficient islets and in beta-TC6 cells transfected with siAtg7 was measured by quantitative real-time polymerase chain reaction. RESULTS: Baseline oxygen consumption rate of Atg7-deficient islets was significantly lower than that of control islets (P<0.05). Intracellular ATP content of Atg7-deficient islets during glucose stimulation was also significantly lower than that of control islets (P<0.05). By Oxygraph-2k analysis, mitochondrial respiration in Atg7-deficient islets was significantly decreased overall, although state 3 respiration and responses to antimycin A were unaffected. The mRNA levels of mitochondrial complexes I, II, III, and V in Atg7-deficient islets were significantly lower than in control islets (P<0.05). Down-regulation of Atg7 in beta-TC6 cells also reduced the expression of complexes I and II, with marginal significance (P<0.1). CONCLUSION: Impairment of autophagy in pancreatic beta-cells suppressed the expression of some mitochondrial respiratory complexes, and may contribute to mitochondrial dysfunction. Among the complexes, I and II seem to be most vulnerable to autophagy deficiency.
Adenosine ; Adenosine Triphosphate ; Animals ; Antimycin A ; Autophagy* ; Down-Regulation ; Glucose ; Insulin-Secreting Cells ; Mice* ; Mitochondria ; Oxygen Consumption ; Real-Time Polymerase Chain Reaction ; Respiration ; RNA, Messenger