Correction of diabetes in an autoimmune model using insulin-secreting liver cells

Project Member(s): Simpson, A., O'Brien, B.

Funding or Partner Organisation: National Health & Medical Research Council (NHMRC Program Grants)

Start year: 2005

Summary: Type I diabetes in humans is caused by the autoimmune destruction of pancreatic beta cells. Current treatment of the disease requires daily injections of insulin to control blood glucose levels. Tight glucose control lowers, but does not eliminate the onset of diabetic complications such as blindness, kidney failure and heart disease, which greatly reduce the quality and longevity of life for patients and cost Australia and nations worldwide countless millions of dollars in patient care. The problem of glucose control could be overcome by genetically engineering "an artificial beta cell" that is capable of synthesising, storing and secreting insulin in response to metabolic signals. The liver cells is an ideal target for such technology as it has similar glucose-sensing apparatus to the pancreatic beta cell. In this research project the scientists have used a microsurgical procedure of portal infusion, in which the liver is segregated from the normal blood supply and a non-infective vector containing human insulin is delivered to the liver of non obese diabetic mice that spontaneously develop diabetes along similar lines to Type I diabetic humans. This has resulted in the reversal of diabetes for 160 days (experimental endpoint). Sections of the livers of these animals developed pancreatic characteristics, such as the development of insulin storage granules and expression of other pancreatic hormones glucagon and somatostatin. The animals responded to increased glucose levels in a normal manner and normal liver function was maintained.

Publications:

Gerace, D, Martiniello-Wilks, R, Nassif, NT, Lal, S, Steptoe, R & Simpson, AM 2017, 'CRISPR-targeted genome editing of mesenchymal stem cell-derived therapies for type 1 diabetes: a path to clinical success?', Stem Cell Research & Therapy, vol. 8, no. 1.
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Gerace, D, Martiniello-Wilks, R, O'Brien, BA & Simpson, AM 2015, 'The use of beta-cell transcription factors in engineering artificial beta cells from non-pancreatic tissue', GENE THERAPY, vol. 22, no. 1, pp. 1-8.
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Simpson, A, Gerace, D & Martiniello-Wilks, R 2015, 'Diabetes reversal via gene transfer: building on successes in animal models', Research and Reports in Endocrine Disorders, vol. 5, pp. 15-15.
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Ren, B, O'Brien, BA, Byrne, MR, Ch'ng, E, Gatt, PN, Swan, MA, Nassif, NT, Wei, MQ, Gijsbers, R, Debyser, Z & Simpson, AM 2013, 'Long‐term reversal of diabetes in non‐obese diabetic mice by liver‐directed gene therapy', The Journal of Gene Medicine, vol. 15, no. 1, pp. 28-41.
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FOR Codes: Gene Therapy, Endocrine organs and diseases (incl. diabetes), Diabetes, Gene and Molecular Therapy, Gene and molecular therapy , Clinical health

Acknowledgement of Country

UTS acknowledges the Gadigal people of the Eora Nation, the Boorooberongal people of the Dharug Nation, the Bidiagal people and the Gamaygal people, upon whose ancestral lands our university stands. We would also like to pay respect to the Elders both past and present, acknowledging them as the traditional custodians of knowledge for these lands.