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Research in our laboratory is focused on metabolic signaling in pancreatic islets of Langerhans. As metabolic sensors for the organism, islets regulate blood glucose by releasing the hormones insulin and glucagon. Our main interests lie in two features of nutrient metabolism in islet cells, (1) the ability to trigger pulses of insulin release, and (2) the ability to fine-tune hormone secretion through islet cell-cell communication. To understand how these processes adapt to environmental stress, it is essential to study islet metabolism in real time. To do so, we utilize mouse models of obesity/diabetes in combination with biochemistry, patch clamp electrophysiology, and quantitative imaging. A central focus of the lab is the use of fluorescence microscopy (3D light-sheet imaging, optogenetics, and 2-photon microscopy) to monitor biochemical reactions as they occur in living cells.
3D imaging of lactate
in islet beta cells.
Time-lapse imaging of islet calcium oscillations that trigger insulin secretion.
Visualizing pancreatic islet metabolism with
2-photon NAD(P)H fluorescence lifetime imaging
Regulation of insulin and glucagon secretion by pyruvate kinase
There are three isoforms of PK expressed in the pancreatic islets cells – constitutively active PKM1, and the dynamically regulated isoforms PKM2 and PKLR. We are working to understand how these crucial glycolytic enzymes control metabolic and electrical activity in alpha and beta cells.
Impacts of age and obesity on islet function
Currently we are studying the effects of two cyclin-dependent kinases, CDK1 and CDK2, on beta cell mitochondrial metabolism and electrical activity. These kinases are responsive to age and obesity, two major risk factors for diabetes.
Nutrient regulation of islet cell-cell communication: 3D lightsheet imaging and optogenetics
To understand precisely how nutrients control hormone secretion, the goals of this project are: 1) measure the activity of every islet cell, 2) manipulate the activity of every cell, and 3) computationally analyze/model these circuits and their failure in diabetes. We've constructed a 3D lightsheet microscope capable of recording biosensors in intact islets at speeds up to 10 Hz, while stimulating or repressing islet cell activity using optogenetics.
Postdoctoral, Ph.D. students, and undergraduates interested in pursuing research in the laboratory should contact Dr. Merrins directly at email@example.com
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