Insulin on the Brain
Dr Garron Dodd
+61 3 9035 3918
A key hallmark of Type-2 Diabetes (T2D) is insulin resistance. People with insulin resistance, have built up a tolerance to insulins action at the insulin receptor, making the hormone less effective and resulting in impaired glucose homeostasis and T2D. The mechanisms underlying insulin resistance are unclear and there are limited therapeutics to treat insulin resistance. Insulin signals to the brain, where it regulates glucose homeostasis by altering the sensitivity of peripheral tissues to insulin. Insulin signals to specialised neurons of the hypothalamus, termed agouti-related peptide (AgRP) and pro-opiomelancortin (POMC) neurons, however, the mechanisms by which the insulin receptor signalling in these neurons controls of glucose homeostasis and how this goes wrong in T2D is unclear.
In this project we will use the latest advancements in pharmaco-genetic neuronal manipulation, in vivo neuronal imaging and CRISPR/Cas9 gene editing to define how insulin signals to AgRP/POMC neurons and how this becomes defective in T2D. Overall, this work aims to uncover novel disease mechanisms and pharmacological targets by which to treat metabolic disease.
Garron Dodd, Head of Laboratory
This research project is available to Honours students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.
Dodd GT, Michael NJ, Mangiafico SP, Pryor JT, Lee-Young RS, Simonds SE, Brüning JC, Cowley MA, Horvath T, Andrikopoulos S, Spanswick D, Tiganis T (2018). POMC neurons differentially respond to insulin to control glucose metabolism. eLife. 19;7. doi: 10.7554/eLife.38704. PMID: 30230471
Dodd GT, Lee-Young RS, Tiganis T (2018). TCPTP in AgRP neurons coordinates hepatic insulin sensitivity and peripheral glucose metabolism via a hypothalamic-liver axis. Diabetes. Apr 30. pii: db171485. doi: 10.2337/db17-1485. PMID: 29712668
Dodd GT, Tiganis T (2017). Insulin in the Brain: Roles in Energy and Glucose Homeostasis. J Neuroendocrinology. doi: 10.1111/jne.12513. PMID: 28758251
Dodd GT, Andrews ZB, Simmonds S, Michael NJ, DaVeer M, Bruning JC, Spanswick D, Cowley MA, Tiganis T (2017). A hypothalamic phosphatase switch coordinates energy expenditure with feeding. Cell Metabolism, 26: 375-393. PMID: 28768176
Dodd GT, Descherf S, Loh K, Simmond S, Wiede F, Mery TL, Zhang Z, Kahn BB, Neel BG, Bence KK, Andrews ZB, Cowley MA, Tiganis T (2015). Leptin and insulin act synergistically on proopiomelanocortin neurons to promote white adipose tissue browning. Cell 160: 88-106. PMID: 25594176
Dodd GT, Worth AA, Nunn N, Korpal AK, Bechtold DA, Allison MB, Myers MG Jr, Statnick MA, Luckman SM (2014). The thermogenic effect of leptin is dependent on a distinct population of prolactin-releasing peptide neurons in the dorsomedial hypothalamus. Cell Metabolism 20: 639-49. PMID: 25176149
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