The six minichromosome maintenance proteins (Mcm2-7) are required for both the initiation and elongation of chromosomal DNA, ensuring that DNA replication takes place once, and only once, during the S phase. Here we report on the cloning of a new human Mcm gene (hMcm8) and on characterisation of its protein product. The hMcm8 gene contains the central Mcm domain conserved in the Mcm2-7 gene family, and is expressed in a range of cell lines and human tissues. hMcm8 mRNA accumulates during G(1)/S phase, while hMcm8 protein is detectable throughout the cell cycle. Immunoprecipitation-based studies did not reveal any participation of hMcm8 in the Mcm3/5 and Mcm2/4/6/7 subcomplexes. hMcm8 localises to the nucleus, although it is devoid of a nuclear localisation signal, suggesting that it binds to a nuclear protein. In the nucleus, the hMcm8 structure-bound fraction is detectable in S, but not in G(2)/M, phase, as for hMcm3. However, unlike hMcm3, the hMcm8 structure-bound fraction is not detectable in G(1) phase. Overall, our data identify a new Mcm protein, which does not form part of the Mcm2-7 complex and which is only structure-bound during S phase, thus suggesting its specific role in DNA replication.

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Parathormone levels were determined in 17 patients with functioning renal transplants. In 8 patients recently transplanted, very high serum levels of parathormone were found without obvious relation to the glomerular filtration rate. Hypophosphatemia was also present in these cases. In 9 other patients studied 2–7 years after transplantation the mean level of parathormone was lower than in the previous group but levels above normal were noted in half of the patients, some of which had perfect renal function and normal serum phosphorus. The response to induced hypercalcemia was used as a sensitive test to reveal abnormal responses even in cases which initially had normal peripheral levels of parathormone. From these results, tertiary hyperparathyroidism would appear to be rare although hyperfunctioning parathyroid glands can be demonstrated long after kidney transplantation, even when renal function is close to normal.

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Introduction: REG3A (Regenerating islet-derived protein 3A) is a carbohydrate-binding protein belonging to the family of C-type lectins. REG3A has antioxidant and anti-inflammatory properties modulating glucose and lipid homeostasis. We report a study of the effects of the administration of the human recombinant REG3A protein ALF-5755 on glucose and lipid homeostasis in insulin-resistant mice. Materials and Methods: 4-week-old C57Bl/6N male mice were fed HFD for 12 weeks. The control group received a standard chow diet. 12-week-old Ob/Ob mice were used. Mice were given ALF-5755 (43µg/day, ALF group) or a formulation buffer (buffer group) by subcutaneous infusion for 28 days. We measured: body weight, blood glucose, fasting insulin, glucose tolerance and insulin sensitivity, glucose turnover and uptake during hyperinsulinemic/euglycemic clamps and AMPK activity. Results: In both models, ALF-5755 administration significantly decreased basal blood glucose with no change in basal insulin levels. The changes in blood glucose levels in response to an oral glucose load in the ALF and buffer groups were similar in HFD-fed mice but were lowered by ALF-5755 in Ob/Ob mice. Insulin secretion at 15 and 30 min was significantly reduced in the ALF group compared to Buffer group in both models. During clamp, glycolytic muscles exhibited an increase in glucose uptake in HFD-fed mice, and an increase in AMPK activity in both models treated with ALF-5755. Insulin sensitivity was increased in ALF group. The plasma TG was significantly decreased in the ALF compared to Buffer group. No difference in body weight was observed whatever the administered molecules. Conclusion: Administration of ALF-5775 improves blood glucose and insulin sensitivity in insulin-resistant mice. This effect is mediated by an increase of skeletal muscle glucose uptake through AMPK activation. REG3A is a potential therapeutic drug for the management of insulin resistance syndrome. Disclosure M. Darnaud: None. C. Cruciani-Guglielmacci: Consultant; Self; The Healthy Aging Company. P. Gonzalez: None. P. Amouyal: None. G. Amouyal: None. L. Jamot: None. N. Moniaux: None. F. Andreelli: Consultant; Self; Lilly Diabetes, THAC. Speaker’s Bureau; Self; Lilly Diabetes. Other Relationship; Self; Lilly Diabetes. C.B. Bréchot: Consultant; Self; Romark. Employee; Self; The Healthy Aging Company. C. Magnan: None. J. Faivre: None.