David Aaron Jacobson
Vanderbilt University, TN·Physiology
In type 2 diabetes, the pancreatic islets, clusters of hormone-making cells, stop responding properly to blood sugar. This contributes to high blood sugar (hyperglycemia).
- Fields
Physiology
Pharmacology
Biochemistry
- Topics
type 2 diabetes
pancreatic islets
β-cells
- Grants
- 3 known grants, through Jun 2029
What they work on
- Determine how the calcium pump PMCA1 and sodium/calcium exchanger NCX1 control β-cell calcium removal and insulin secretion, and how diabetes alters them, using β-cell knockout mice and human pseudoislets with shRNA knockdown.
- Determine how PMCA1 and NCX1 regulate α-cell calcium handling and glucagon secretion, and whether their reduced activity under diabetic conditions drives α-cell dysfunction, using α-cell knockout mice and human pseudoislets.
- Test whether Src tyrosine kinase activation and PKA inhibition of the Na+/K+-ATPase (NKA) control β-cell membrane voltage, calcium entry and insulin secretion, using mice and human β-cells lacking NKA subunits.
- Determine how NKA shapes δ-cell calcium handling and somatostatin secretion, and how reduced NKA function under diabetic stress causes δ-cell dysfunction, using δ-cell knockout mice and human pseudoislets.
- Test whether the calcium-sensing receptor CaSR amplifies glucose-stimulated ER calcium release and somatostatin secretion in δ-cells, using δ-cell CaSR knockout mice and human pseudoislets with CaSR knockdown.
- Determine how the ER potassium channel TALK-1 limits δ-cell calcium storage and contributes to dysfunction in diabetes, using δ-cell TALK-1 knockout mice and human pseudoislets expressing dominant-negative TALK-1.
More about the research
Islet cells release hormones when calcium levels inside them rise: insulin from β-cells, glucagon from α-cells and somatostatin from δ-cells. Calcium entry is controlled by the cell's membrane voltage and by internal calcium stores. The lab's three projects ask how ion pumps, exchangers, channels and receptors set these calcium signals, and how diabetic conditions disrupt them.
Why it matters
By identifying how calcium pumps, exchangers, channels and receptors control insulin, glucagon and somatostatin release, and how they fail in type 2 diabetes, this work could reveal new therapeutic targets and drug strategies. These could help restore normal islet hormone secretion and blood sugar control in people with type 2 diabetes.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Calcium Extrusion in the Context of Pancreatic Islet Function and Dysfunction
NIH · Aug 2025 – Jun 2029
Secretagogue and Gi/o-GPCR signaling through the islet Na+/K+-ATPase in health and diabetes
NIH · Aug 2023 – Apr 2027
Molecular Mechanisms Regulating Pancreatic Delta Cell Function and Dysfunction
NIH · Apr 2022 – Jan 2027
Closest labs
Michelle Kimple
University of Wisconsin-Madison, WI·Pharmacology
Determine how the EP3 receptor affects separate cellular pools of calcium and cAMP in mouse and human beta cells, and how these changes alter insulin secretion and beta-cell mass, using cellular imaging.
Bethany Cummings
University of California-Davis, CA·Physiology
Compare liver and islet responses to injected glucagon in obese mice and after dietary or bariatric-surgery weight loss, to test whether α-cell signaling shifts from the liver to insulin secretion.
Barak Blum
University of Wisconsin-Madison, WI·Physiology
Test the hypothesis that reducing Robo2 receptors in beta cells, the pancreas's insulin-making cells, is essential for islets of Langerhans to expand successfully when insulin demand rises.
The school
Vanderbilt University: 22 labs on PI Pages, $1.3B a year on research, 494 research doctorates a year.
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