Type 1 Diabetes:An Application of Molecular Biology

Katie Kesler

What is Diabetes?

Diabetes metillus is a metabolic disorder where the body does not make or respond to insulin

Insulin is a peptide hormone that causes glucose to brought into the cell faster

Photo credit: https://www.asu.edu/courses/css335/images/diabetessymptoms.gif

Symptoms of Diabetes

Type 1 vs. Type 2

Type 1 Also called Insulin-

dependent diabetes or juvenile diabetes

Rapid onset

Autoimmune disease

Several possible causes or risk factors

Type 2 Slow onset

Characterized by insulin resistance

Has some known risk factors

Human Leukocyte Antigen (HLA)

Class I

Class II HLA-DP

HLA-DQ

HLA-DR

Class III

Why is this so

hard?Photo credit: Google Images

Source: Kelly, et al. Molecular aspects.

Source: Djoulah et al. A new predictive model for IDDM susceptibility.

Discovery of Insulin

1869: Paul Langerhans discovers islet cells.

1920: Frederick Banting talks John James MacLeod into funding his insulin research. MacLeod pairs him up with Charles Best.

1921: Best and Banting finally obtain insulin by switching to an alcohol preparation of the pancreas.

1922: James Collip joins the team, and is able to purify insulin using a 90% alcohol solution to precipitate the proteins.

1922: Eli Lilly and George Walden begin producing insulin commercially. Walden discovers link between degradation and pH. He begins precipitating insulin at its isoelectric point.

Photo credit: diabetesmanager.pbworks.com

Structure of Proinsulin

Discovery of Insulin

Photo credit: www.industry.siemens.com/topics/global/

Insulin in Plants

Insulin in Fungi

Photo credit: Google Images

Saccharomyces cerevisiae Pichia pastoris

References

Alam, T., Wai, P., Held, D., Vakili, S. T., Forsberg, E., & Sollinger, H. (2013, June). Correction of Diabetic Hyperglycemia and Amelioration of Metabolic Anomalies by Minicircle DNA Mediated Glucose Dependent Hepatic Insulin Production. PLOS One, 8(6), 1-10.

Djoulah, S., Busson, M., Sasazuki, T., Maillere, B., Yasunaga, S., Kimura, A., . . . Hors, J. (1999). A new predictive model for insulin-dependent diabetes metllitus susceptibility based on combinations of molcular HLA-DRB1 and HLA-DQB1 pockets. Tissue Antigens, 54, 341-348.

Goodsell, D. (2006, May). Glucose Oxidase. Retrieved November 14, 2015, from RCSB Protein Data Bank: http://www.rcsb.org/pdb/101/motm.do?momID=77

HLA gene family. (2009, February). (NIH) Retrieved November 13, 2015, from Genetics Home Reference: http://ghr.nlm.nih.gov/geneFamily/hla

Insulin Analog. (2014, May 6). Retrieved November 14, 2015, from Diabetes Self-Management: http://www.diabetesselfmanagement.com/diabetes-resources/definitions/insulin-analog/

Insulin Analogs. (n.d.). (UCSF) Retrieved November 14, 2015, from Diabetes Education Online: http://dtc.ucsf.edu/types-of-diabetes/type2/treatment-of-type-2-diabetes/medications-and-therapies/type-2-insulin-rx/types-of-insulin/insulin-analogs/#rapid

Insulin-regulated movement of GLUT4. (n.d.). Retrieved November 12, 2015, from http://weill.cornell.edu/biochem/mcgraw/insulin-regulated.html

Johnson, I. S. (1983, February 11). Human Insulin from Recombinant DNA Technology. Science, 219(4585), 632-637.

Kelly, M. A., Rayner, M. L., Mijovic, C. H., & Barnett, A. H. (2003). Molecular aspects of type 1 diabetes. Journal of Clinical Pathology: Molecular Pathology, 56, 1-10.

References

Kelly, M. A., Rayner, M. L., Mijovic, C. H., & Barnett, A. H. (2003). Molecular aspects of type 1 diabetes. Journal of Clinical Pathology: Molecular Pathology, 56, 1-10.

Nykiforuk, C. L., Boothe, J. G., Murray, E. W., Keon, R. G., Goren, H. J., Markely, N. A., & Moloney, M. M. (2005). Transgenic expression and recovery of biologically active recombinant human insulin from arabidopsis thaliana seeds. Plant Biotechnology Journal, 3, 1-9.

Oliver, N. S., Toumazou, C., Cass, A. E., & Johston, D. G. (2009). Glucose sensors: a review of curent and emerging technology. Diabetic Medicin, 26, 197-210.

Poicot, F., & McDermott, M. F. (2002). Genetics of type 1 diabetes metllitus. Genes and Immunity, 3, 235-249.

Rosenfeld, L. (2002). Insulin: Discovery and Controvery. Clinical Chemistry, 48(12), 2270-2288.

Stretton, A. O. W. (2002). The First Sequence: Fred Sanger and Insulin. Genetics, 162(2), 527-532.

Szablewski, L. (2014, June 30). Role of immune system in type 1 diabetes metllitus pathogenesis. International Immunopharmacology, 22, 182-191.

Thim, L., Hansen, M. T., Norris, K., Hoegh, I., Boel, E., Forstrom, J., . . . Fiil, N. P. (1986, September). Secretion and processing of insulin precursors in yeast. Proceedings of the National Academy of Sciences, 83, 6766-6770.

Wang, Y., Liang, Z. H., Zhang, Y. S., Yao, S. Y., Xu, Y. G., Tang, Y. H., . . . Feng, Y. M. (2001, April 5). Human Insulin from a Precursor Overexpressed in the Methylotrophic Yeast Pichia pastoris and a Simple Procedure for Purifying the Expressing Product. Biotechnology and Bioengineering, 73(1), 74-79.

WebMD. (2015). Diabetes Health Center. Retrieved November 12, 2015, from WebMD: http://www.webmd.com/diabetes/guide/default.htm