Our Research Members

Research in the Gaisano lab is focused on molecular mechanisms regulating exocytosis, employing islet cells as models. We were one of the firsts to demonstrate that SNARE proteins originally found to mediate neurotransmitter release are conserved in non-neuronal cells, including the pancreatic islet to regulate secretion. We contributed to the original work showing SNARE protein regulation of insulin granule exocytosis, and subsequently contributed much of the work showing how SNARE proteins physically and functionally interact with beta-cell ion channels (Kv, KATP, Ca2+) to regulate the intricate sequence of ion fluxes, membrane potential and exocytotic fusion events leading to secretion.  Current efforts are a continuation of the above (1 and 2) plus two new directions (3 and 4).  1) SNAREs interactions with Kv and Ca2+ channels forming ‘excitosomes’ and how these excitosomes are involved in the insulin granule exocytotic machinery for predocked (first phase insulin secretion) and newcomer granules (second phase insulin secretion); and how these insights could reveal rescue strategies for T2D insulin secretory deficiency. 2) Islet alpha cell secretory mechanisms and crosstalk with beta- and delta-cells in health and their dysregulation in T1D.  For these 2 directions, we are using human T1D and T2D pancreas as well as normal human pancreas.  3) Using the transparent anterior chamber of the mouse eye, we are observing the behaviour of implanted human islets, a capability that we directing at assessing human T1D and T2D islet biology over a long duration, their responses to novel treatment strategies, and also islet regenerative medicine.  4) Role of the intestinal microbiome in its contribution to the pathogenesis of the metabolic syndrome, and identifying new treatment strategies. The Gaisano lab has in place a full spectrum of state-of-the-art technologies to assess these four funded directions. 

The primary theme of A.G.’s research is the investigation of the effects of excess circulating energy substrates, in particular free fatty acids, on insulin action, secretion and kinetics, and the implication of these effects for the pathogenesis of diabetes. Secondary themes of research are the studies of the effects of nutrient and insulin excess in animal models of atherosclerosis and cancer .

Research in the Gilbert lab focuses on the pathogenesis of diabetes complications as a way to evolve new therapies to prevent their development and attenuate their progression. Current projects involve translational research in diabetic nephropathy, retinopathy and heart failure, exploring novel pharmacological treatments and the use of adult stem cells to regenerate diseased tissue.

I am interested in understanding how exercise and nutrition impact carbohydrate and fat metabolism in humans, and identifying lifestyles strategies to improve metabolic health. This ranges from conducting studies in young healthy adults to those at risk for, or afflicted with, metabolic disease. We are interested in practical questions relating to the importance of exercise dose (e.g., intensity vs. duration), mode (e.g., aerobic vs. resistance), and timing (e.g., before vs. after a meal) on indices of metabolic health such as insulin sensitivity and cardiorespiratory fitness. We are also interested in exploring sex-based differences in the adaptive response to exercise and nutritional interventions in an effort to provide sex-specific recommendations for improved health of Canadians.

We study the role of a mitochondrial named NLRX1 in diabetes. Our preliminary research has identified that NLRX1 plays a role in the regulation of body weight and of obseity-induced diabetes in vivo. Because NLRX1 was identified as a key regulator of apoptosis during inflammation, we are interested in identifying how this mitochondrial protein links obesity and diabetes with inflammation and cell death.

Diabetes in primary care – processes of care, impact of incentives, health disparities.
Risk factors for diabetes, especially socioeconomic status, ethnoracial background and immigration, neighbourhood walkability.

Our research focuses on the effects of diabetes on the skeletal system using pre-clinical models. Examples of our research includes:

1) Effect of Vanadium Treatment on Bone Loss and Bone Quality in Rat Models of Diabetes. Vanadium compounds have been shown to be effective in experimental diabetes and insulin-resistant hypertension. However, these agents are known to accumulate in bone mineral where vanadate substitutes for phosphate. It is therefore essential to understand the long-term effects on these compounds on bone quality. (Facchini DM, Yuen VG, Battell ML, McNeill JH, Grynpas MD. The effects of vanadium treatment on bone in diabetic and non-diabetic rats. Bone. 2006; 38(3):368-77)

2) The effect of Rosiglitazone treatment on bone quality in rat models of type 2 diabetes and osteoporosis. Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat patients with Type 2 Diabetes Mellitus (T2DM) to improve glycemic control. The ADOPT clinical trial showed that women taking RSG experienced more fractures. The purpose of our study is to understand the mechanism by which RSG induces limb fracture and alters bone quality in the insulin resistant Zucker Fatty rat.

3) Comparison of the skeletal effects in the treatment of type2 diabetes with Sitagliptin (a DPP4 inhibitor) or Pioglitazone (a PPRgamma agonist) in mice fed a high fat diet.