2020 Brosnan Lecture in Biochemistry

The journey of insulin through the body: from secretion to action

Amira Klip, Ph.D.
Senior Scientist and Professor
The Hospital for Sick Children (SickKids) and
The University of Toronto

Insulin is the paramount anabolic hormone, promoting carbon energy deposition in the body*. Its biosynthesis, quality control, delivery, and action are exquisitely regulated by highly orchestrated intracellular mechanisms in different organs along its journey. In this presentation, I will outline five stages of the journey of insulin through the body and the cell biology that underlies the interaction of insulin with each organ. I will first analyze insulin’s biosynthesis in and export from pancreatic β-cells. Next, its first pass and partial clearance in the liver with its temporality and periodicity linked to secretion. Continuing the journey, I will briefly describe insulin’s action on the blood vasculature and its still-debated mechanisms of exit from the capillary beds. Once in the parenchymal interstitium of muscle and adipose tissue, insulin promotes glucose uptake into myofibres and adipocytes, and I will elaborate on the intricate signalling and vesicle traffic mechanisms that enable this fundamental function. Cellular discernment of insulin’s availability and action should prove critical to understanding its pivotal physiological functions and how their failure leads to diabetes.

*This abstract is adapted from Tokarz, MacDonald and Klip (2018) The Cell Biology of Systemic Insulin Function. J Cell Biol 217 (7): 2273–2289, http://doi.org/10.1083/jcb.201802095

Meeting information:
November 24th, 12-1pm
Graduate students are welcome to stay for a meet the speaker session 1-2pm

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