Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Role of alpha-beta cell communication in the functional heterogeneity of beta cells in health and T2D

Award Number: R01DK148909
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

Group Awards By:

View Award Description

Role of alpha-beta cell communication in the functional heterogeneity of beta cells in health and T2D - Vira Kravets, PhD R01 Abstract Type 2 diabetes (T2D) is marked by progressive beta cell dysfunction, but emerging evidence indicates this failure is not uniform. Our group and others have identified functionally distinct beta cell subpopulations—“first responders” and “leaders”—that initiate and coordinate the islet’s biphasic insulin response. These cells contribute disproportionately to insulin secretion and play essential roles in islet coordination. Yet, the mechanisms governing their emergence remain poorly understood. This project addresses three major knowledge gaps: - the role of alpha-cell–mediated GLP-1 receptor (GLP-1R) signaling in shaping beta cell heterogeneity, - the effect of beta cell proximity to alpha cells on local gene expression, and - the selective vulnerability of these subpopulations to T2D. We hypothesize that alpha-to-beta paracrine signaling—primarily via GLP-1 and glucagon— creates spatial microenvironments that reprogram neighboring beta cells both metabolically and transcriptionally, predisposing them to dysfunction in T2D. Aim 1 will quantify how GLP-1R and downstream PKA signaling contribute to beta cell heterogeneity. We will use optical Ca²⁺ imaging, Phasor-FLIM NAD(P)H readouts, and PKA sensors in live human and mouse pancreatic slices to evaluate how alpha-cell secretions drive differential beta cell activation. Pharmacological blockade and transgenic models will test the roles of GLP-1R and glucagon receptor signaling. In-silico modeling will complement experimental data. Aim 2 will define the role of alpha cells in shaping beta cell subpopulations that are preferentially vulnerable in T2D. We will combine functional imaging with spatial transcriptomics in pancreatic slices from non-diabetic (ND) and T2D donors. Our preliminary data show enhanced oxidative phosphorylation, insulin/IAPP expression, and glucose responsiveness in alpha-proximal beta cells. We also found greater dysfunction in T2D donor tissue and in islets with higher alpha-cell content. Our integrated approach—merging live functional imaging, spatial transcriptomics, and computational modeling—will clarify how paracrine signaling and spatial islet architecture shape beta cell heterogeneity. By identifying subpopulation-specific failure patterns in T2D, this work will move the field beyond the current view of beta cell failure as uniform or stochastic. Impact: This research may reveal early biomarkers of islet dysfunction, optimize GLP-1R–based therapies, and inform the design of stem-cell–derived islets with improved resilience for transplantation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $501,246 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/2/2026	NEW	$501,246
														Subtotal = $501,246

Grand Total All Awards = $501,246

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of alpha-beta cell communication in the functional heterogeneity of beta cells in health and T2D

Award Number: R01DK148909

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer