It has long been recognized that vitamin D deficiency is associated with muscle weakness and falls. Vitamin D receptor (VDR) is present at very low levels in normal muscle. Whether vitamin D plays a direct role in muscle function is unknown and is a subject of hot debate. Myocyte-specific deletion of VDR would provide a strategy to answer this question. Myocyte-specific vitamin D receptor (mVDR) null mice were generated by crossing human skeletal actin-Cre mice with floxed VDR mice. The effects of gene deletion on the muscle phenotype were studied in terms of body tissue composition, muscle tissue histology, and gene expression by real-time PCR. This study demonstrates that vitamin D signalling is needed for myocyte function. Despite the low level of VDR protein normally found muscle, deleting myocyte VDR had important effects on muscle size and strength. Maintenance of normal vitamin D signalling is a useful strategy to prevent loss of muscle function and size.

C Girgis, KM Cha, B So, M Tsang, J Chen, PJ Houweling, A Schindeler, RA Stokes, MM Swarbrick, FJ Evesson, ST Cooper, JE Gunton. Journal of Cachexia, Sarcopenia and Muscle, 2019; 10: 1228-1240.

Gunton JE. J Clin Invest. 2020 Oct 1;130(10):5063-5073.

The development of autoimmune disease type 1 diabetes (T1D) is determined by both genetic background and environmental factors – including RNA viruses, particularly coxsackievirus (CV) – but how they induce T1D is not understood. Here, we demonstrate that deletion of the transcription factor hypoxia-inducible factor-1α (HIF-1α) from β cells increases the susceptibility of non-obese diabetic (NOD) mice to environmentally triggered T1D from coxsackieviruses and the β cell toxin streptozotocin. Studies in coxsackievirus-infected islets demonstrate that lack of HIF-1α leads to impaired viral clearance, increased viral load, inflammation, pancreatitis, and loss of β cell mass. The findings show an important role for β cells and, specifically, lack of β cell HIF-1α in the development of T1D.

Lalwani A, Warren J, Liuwantara D, Hawthorne WJ, O’Connell PJ, Gonzalez FJ, Stokes RA, Chen J, Laybutt DR, Craig ME, Swarbrick MM, King C, Gunton JE. Cell Rep. 2019 May 21;27(8):2370-2384.e6.

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts’ recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients.

Boggi U, Vistoli F, Andres A, Arbogast HP, Badet L, Baronti W, Bartlett ST, Benedetti E, Branchereau J, Burke GW 3rd, Buron F, Caldara R, Cardillo M, Casanova D, Cipriani F, Cooper M, Cupisti A, Davide J, Drachenberg C, de Koning EJP, Ettorre GM, Fernandez Cruz L, Fridell JA, Friend PJ, Furian L, Gaber OA, Gruessner AC, Gruessner RWG, Gunton JE, Han DJ, Iacopi S, Kauffmann EF, Kaufman D, Kenmochi T, Khambalia HA, Lai Q, Langer RM, Maffi P, Marselli L, Menichetti F, Miccoli M, Mittal S, Morelon E, Napoli N, Neri F, Oberholzer J, Odorico JS, Öllinger R, Oniscu G, Orlando G, Ortenzi M, Perosa M, Perrone VG, Pleass H, Redfield RR, Ricci C, Rigotti P, Paul Robertson R, Ross LF, Rossi M, Saudek F, Scalea JR, Schenker P, Secchi A, Socci C, Sousa Silva D, Squifflet JP, Stock PG, Stratta RJ, Terrenzio C, Uva P, Watson CJE, White SA, Marchetti P, Kandaswamy R, Berney T.

Am J Transplant. 2021 Sep;21 Suppl 3(Suppl 3):17-59.

Chronic foot ulcers are associated with a high risk of osteomyelitis, poor quality of life, amputations and disability. Few strategies improve their healing, and amputation rates in high-risk foot services are usually over 30 %. We conducted a randomised, inactive-placebo controlled, double-blind trial of 500 mg of slow-release vitamin C in sixteen people with foot ulcers in the Foot Wound Clinic at Westmead Hospital. Healing at 8 weeks was significantly better in the vitamin C group. Healing without amputation occurred in all patients in the vitamin C group. In contrast, 44 % of controls had not healed their ulcer at the end of the study period. Vitamin C improved healing of foot ulcers. Further studies are needed to determine whether there is a threshold effect for serum vitamin C above which therapy is ineffective and whether there are better or lesser responding subgroups. Because of its low cost and ease of access and administration, we recommend offering vitamin C.

Gunton JE, Girgis CM, Lau T, Vicaretti M, Begg L, Flood V. Br J Nutr. 2021 Nov 28;126(10):1451-1458.