We tested the hypothesis that liver protein kinase C (PKC) is increased in non-insulin-dependent diabetes mellitus (NIDDM). To this end we examined the distribution of PKC isozymes in liver biopsies from obese individuals with and without NIDDM and in lean controls. PKC isozymes a, 13, e and g were detected by immunoblotting in both the cytosol and membrane fractions. Isozymes y and 6 were not detected. There was a significant increase in immunodetectable PKC-a (twofold), -E (threefold), and -C (twofold) in the membrane fraction isolated from obese subjects with NIDDM compared with the lean controls. In obese subjects without NIDDM, the amount of membrane PKC isozymes was not different from the other two groups. We next sought an animal model where this observation could be studied further. The Zucker diabetic fatty rat offered such a model system. Immunodetectable membrane PKC-ci, -13, -e, and -t were significantly increased when compared with both the lean and obese controls. The increase in immunodetectable PKC protein correlated with a 40% elevation in the activity of PKC at the membrane. Normalization of circulating glucose in the rat model by either insulin or phlorizin treatment did not result in a reduction in membrane PKC isozyme protein or kinase activity. Further, phlorizin treatment did not improve insulin receptor autophosphorylation nor did the treatment lower liver diacylglycerol. We conclude that liver PKC is increased in NIDDM, a change that is not secondary to hyperglycemia. It is possible that PKCmediated phosphorylation of some component in the insulin signaling cascade contributes to the insulin resistance observed in NIDDM. (J. Clin. Invest. 1995Invest. .95:2938Invest. -2944

The results of transplantation of free autologous fat obtained by blunt syringe suction lipectomy are unpredictable. We examined if adipose tissue viability is compromised by using syringe suction lipectomy and by infiltration of the tissue with local anesthetics. As reference, we used adipose tissue samples excised during elective surgery. Fat obtained intraoperatively and by lipectomy was digested with collagenase to isolate adipocytes. The mechanical damage associated with sample handling and cell isolation in both procedures was similar and did not exceed 6% of the total cell mass. In addition, cells isolated from intraoperative and lipectomy samples did not differ functionally, responded similarly to insulin stimulation of glucose transport and epinephrine-stimulated lipolysis, and retained the same growth pattern in culture. Since during fat transplantation the graft is exposed to local anesthetics at both the donor and the recipient sites, we reexamined adipocyte function in the presence of lidocaine. Lidocaine potently inhibited glucose transport and lipolysis in adipocytes and their growth in culture. That effect, however, persisted only as long as lidocaine was present; after washing, the cells were able to fully regain their function and growth regardless of whether the exposure was as short as 30 minutes or as long as 10 days. These results indicate that adipose tissue obtained by syringe lipectomy consists of fully viable and functional adipocytes, but local anesthetics may halt their metabolism and growth.

A nutritional survey and evaluation was made in Huntington disease patients by the 24-h-recall method. Control subjects and choreic patients consumed a diet that supplied all the essential amino acids. The diet was hypocaloric, rich in animal protein, and low in fat and carbohydrates. The ratio of calcium to phosphorus in the groups studied was less than 1. High vitamin A and low vitamin C and niacin intakes were observed in Huntington disease patients. Only 17% of control subjects showed weight deficiency; 55% of the patients at stages III and IV of the disease were malnourished despite receiving the same food intake as controls. Although iron intake was deficient in all groups studied, it was enough to maintain normal serum levels of this metal. The deficiencies found in some nutrients do not explain the clinical manifestations observed in Huntington disease patients.

We developed a double-chamber system in which to examine the effects of mature adipocytes on the growth and differentiation of preadipocytes and other cells in the adipose tissue. In the present study we found that mature adipocytes from both lean and obese subjects release a factor that stimulates the growth of preadipocyte-enriched and dedifferentiated adipocyte-enriched cell cultures. This growth stimulation was dependent on both time of exposure to mature cells and the number of mature cells in the coculture. Proliferation of the preadipocyte-enriched (n = 4) and dedifferentiated adipocyte-enriched cultures (n = 5) in the presence of mature adipocytes from obese subjects [body mass index (BMI) > 35] was 4.1- and 2.9-fold more (P < 0.05) than that in the presence of adipocytes from lean subjects (BMI < or = 25). There was no difference in the growth of cultures enriched in preadipocytes or dedifferentiated adipocytes from lean or obese subjects in the absence of mature adipocytes. These observations demonstrate that mature adipocytes from obese patients stimulate the growth of preadipocyte-enriched cultures to a greater extent than those from lean individuals.

Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.

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