Evidence mapPaperPMID 41511443Full record

ArticleDiabetes2026

Paracrine Hormonal Signals From Islet α-Cells Regulate Microtubule Dynamics in β-Cells to Promote Insulin Secretion in Mouse and Human Islets.

Kung-Hsien Ho, Syed N Barmaver, Shannon E Gibson, Ruiying Hu, Mahircan Yagan, Hamida K Ahmed, Appakalai N Balamurugan, David A Jacobson, Irina Kaverina, Guoqiang Gu

Abstract read
In one paragraph

Article in Diabetes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Kung-Hsien HoDepartment of Cell and Developmental Biology, Program in Developmental Biology, Vanderbilt University, Nashville, TN.
Syed N BarmaverDepartment of Cell and Developmental Biology, Program in Developmental Biology, Vanderbilt University, Nashville, TN.
Shannon E GibsonDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
Ruiying HuDepartment of Cell and Developmental Biology, Program in Developmental Biology, Vanderbilt University, Nashville, TN.
Mahircan YaganDepartment of Cell and Developmental Biology, Program in Developmental Biology, Vanderbilt University, Nashville, TN.
Hamida K AhmedDepartment of Cell and Developmental Biology, Program in Developmental Biology, Vanderbilt University, Nashville, TN.
Appakalai N BalamuruganWendy Novak Diabetes Institute, Norton Children's Research Institute, Norton Healthcare, Louisville, KY.
David A JacobsonDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
Irina KaverinaDepartment of Cell and Developmental Biology, Program in Developmental Biology, Vanderbilt University, Nashville, TN.ORCID 0000-0002-4002-8599
Guoqiang GuDepartment of Cell and Developmental Biology, Program in Developmental Biology, Vanderbilt University, Nashville, TN.ORCID 0000-0003-0772-9139

Funding

Calcium Extrusion in the Context of Pancreatic Islet Function and DysfunctionR01DK144192 · VANDERBILT UNIVERSITY · 2025 to 2025
$631k
Myt1 Function for Endocrine Islet Development &FuctionR01DK065949 · VANDERBILT UNIVERSITY · 2004 to 2005
$529k
Secretagogue and Gi/o-GPCR signaling through the islet Na+/K+-ATPase in health and diabetesR01DK136768 · VANDERBILT UNIVERSITY · 2025 to 2025
$506k
Molecular Mechanisms Regulating Pancreatic Delta Cell Function and DysfunctionR01DK129340 · VANDERBILT UNIVERSITY · 2025 to 2025
$450k
Dynamic architecture and function of microtubule networksR35GM127098 · VANDERBILT UNIVERSITY · 2025 to 2025
$436k
CISR CA68485CISR DK20593CISR DK58404CISR DK59637CISR EY08126NIDDK NIH HHS DK106228NIDDK NIH HHS DK125696NIDDK NIH HHS DK128710NIDDK NIH HHS R01 DK065949NIDDK NIH HHS R01 DK106228NIDDK NIH HHS R01 DK125696NIDDK NIH HHS R01 DK128710NIDDK NIH HHS R01 DK129340NIDDK NIH HHS R01 DK136768NIDDK NIH HHS R01 DK144192NIGMS NIH HHS R35 GM127098
6 · The paper itself

Abstract

The microtubule network in β-cells attenuates insulin secretion by pulling insulin secretory granules away from the plasma membrane. Thus, high-glucose-induced microtubule remodeling is required for robust glucose-stimulated insulin secretion. We now demonstrate that hormones secreted by α-cells regulate microtubule dynamics in β-cells through receptors for glucagon (GcgR) and glucagon-like peptide 1 (GLP-1R). Activation of GcgR or GLP-1R destabilizes microtubules in β-cells, accompanied by increased insulin secretion. In contrast, inhibiting these receptors attenuates high-glucose-induced microtubule destabilization and decreases secretion. Supporting the physiological significance of this regulation, β-cells in islets with a higher α-cell-to-β-cell ratio exhibit more dynamic microtubules than those with a lower ratio, and a high-fat diet challenge in mice, which can compromise β-cell secretion, attenuates this effect in their islets. Within individual islets, β-cells located near α-cells show faster microtubule remodeling upon glucose stimulation than those more distant from α-cells. Consequently, islets with a higher α-cell-to-β-cell ratio secrete more insulin in response to glucose stimulation and plasma membrane depolarization, results recapitulated by exogenous glucagon stimulation or chemically induced microtubule destabilization in islets with lower α-cell-to-β-cell ratios. These combined results suggest that α-cells use glucagon-mediated and/or GLP-1-mediated paracrine signaling to fine-tune β-cell secretion via microtubule remodeling. ARTICLE HIGHLIGHTS: Glucagon/glucagon-like peptide 1 sensitizes glucose-induced microtubule remodeling in β-cells. Microtubule density in islets inversely correlates with the α-cell-to-β-cell ratio. Glucose-stimulated insulin secretion levels in single islets positively correlate with their α-cell-to-β-cell ratio. Glucagon and microtubule destabilization mobilize the same granule pool.

Indexed as

Glucagon-Secreting CellsInsulinInsulin-Secreting CellsMicrotubulesParacrine CommunicationAnimalsGlucagonGlucagon-Like Peptide-1 ReceptorGlucoseHumansInsulin SecretionIslets of LangerhansMaleMiceMice, Inbred C57BLReceptors, GlucagonGlucagonGlucagon-Like Peptide-1 ReceptorGlucoseInsulinReceptors, Glucagon

Identifiers

PMID41511443
PMCPMC12928739

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.