Pacific Institute for the Mathematical Sciences - PIMS

Diabetes Double Bill

Speaker: Vipul Periwal

"Dynamics of Adipose Tissue Growth"

Abstract:

Adipose tissue grows by two mechanisms: hyperplasia (cell number
increase) and hypertrophy (cell size increase). Genetics and diet
affect the relative contributions of these two mechanisms to the growth
of adipose tissue in obesity. To address adipose tissue growth
precisely, we developed a mathematical model describing the evolution
of the adipose cell-size distributions as a function of the increasing
fat pad mass, instead of the increasing chronological time. Our model
describes the recruitment of new adipose cells and their subsequent
development in different strains, and with different diet regimens,
with common mechanisms, but with diet- and genetics-dependent model
parameters. Hyperplasia is enhanced by high-fat diet in a
strain-dependent way, suggesting a synergistic interaction between
genetics and diet. Moreover, high-fat feeding increases the rate of
adipose cell size growth, independent of strain, reßecting the increase
in calories requiring storage. Additionally, high-fat diet leads to a
dramatic spreading of the size distribution of adipose cells in both
strains; this implies an increase in size ßuctuations of adipose cells
through lipid turnover.

Speaker: Will Heuett

"Modeling Metabolism in Pancreatic Beta-Cell Mitochondria"

Abstract:

Pancreatic beta-cells sense the ambient blood-glucose
concentration and secrete insulin to signal other tissues to take up
glucose. Mitochondria play a key role in this response as they
metabolize nutrients to produce ATP and reactive oxygen species (ROS),
both of which are involved in insulin secretion signaling. I will
present a model of beta-cell mitochondrial respiration, ATP synthesis,
and ROS production in response to glucose and fatty acid stimulation,
based on available data in the literature and mathematical models
derived from first principles. The model explains experimental
observations of the non-ohmic rise in the passive proton-leak rate at
high membrane potential and its dependence on increased ROS production.
It also predicts that glucose-stimulated insulin secretion is inhibited
by long-term fatty acid exposure, but can be enhanced by inhibiting
uncoupling protein activation and promoting mitochondrial biogenesis.
Using glucose and fatty acid profiles from individuals, I will show
that there is a negative correlation between the amount of ROS produced
per ATP, as predicted by the model, and the individual insulin
sensitivities. Finally, I will discuss how the model can be used to
predict the c-peptide and insulin secretion rate and provide a
quantitative description of beta-cell function for a single individual.
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3:00pm-4:30pm, WMAX 216