Evidence mapPaperPMID 42336059Full record

ArticleMolecular metabolism2026

Heterogeneous expression patterns of the T2D-associated kinesin-4 KIF21A in pancreatic islet endocrine cells.

Syed N Barmaver, Nala Hamilton, Guoqiang Gu, Irina Kaverina

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Article in Molecular metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

4 authors.

Syed N BarmaverDepartment of Cell & Developmental Biology, Vanderbilt University School of Medicine, 552 Engineering & Science Building, 2414 Highland Ave, Nashville, TN, USA.
Nala HamiltonDepartment of Cell & Developmental Biology, Vanderbilt University School of Medicine, 552 Engineering & Science Building, 2414 Highland Ave, Nashville, TN, USA.
Guoqiang GuDepartment of Cell & Developmental Biology, Vanderbilt University School of Medicine, 552 Engineering & Science Building, 2414 Highland Ave, Nashville, TN, USA. Electronic address: guoqiang.gu@Vanderbilt.Edu.
Irina KaverinaDepartment of Cell & Developmental Biology, Vanderbilt University School of Medicine, 552 Engineering & Science Building, 2414 Highland Ave, Nashville, TN, USA. Electronic address: irina.kaverina@vanderbilt.edu.

Funding

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6 · The paper itself

Abstract

backgroundThe β cells in the pancreatic endocrine islets preferentially secrete insulin in specific subdomains of the plasma membrane adjacent to the vasculature (i.e., hot spots). Impaired insulin secretion and β -cell dysfunction are central features of Type-2 Diabetes, yet the cytoskeletal machinery that supports directional secretion and secretory hot spots remains incompletely defined. KIF21A is a plus-end-directed kinesin-4 motor protein that anchors microtubule plus ends to the cell cortex. However, the role of KIF21A in pancreatic islet endocrine cells and potential link to type 2 diabetes (T2D) remain unexplored.

methodsKIF21A mRNA and protein levels were analyzed using bulk RNA-seq and single-cell RNA-seq data using proteomics databases. Kif21a protein distribution was assessed by immunofluorescence in isolated mouse islets using super-resolution microscopy. Likewise, immunostaining of insulin, glucagon, somatostatin, laminin, and detyrosinated tubulin is also performed.

resultsWe show that KIF21A is downregulated in T2D human islets at both the mRNA (RNA-seq) and protein (quantitative proteomics) levels. We also demonstrate cell-type-specific enrichment of Kif21a protein (δ > α > β) in intact islets, confirming the hierarchy suggested by single-cell transcriptomics. We also show that within each endocrine lineage, Kif21a protein shows pronounced cell-to-cell heterogeneity, consistent with endocrine sub-states and functional specialization. And most importantly, we show that implicating Kif21a is spatially enriched at the rosettes and laminin-rich interfaces at vasculature-oriented secretion sites (hot spots), where microtubule anchoring is expected to shape targeted granule delivery.

conclusionsKIF21A is a T2D-associated gene with cell-type-specific and heterogeneous expression in islet endocrine cells. KIF21A may have a cortical microtubule-anchoring function and may contribute to the directed granule delivery to the vasculature for regulated hormone secretion.

Indexed as

Diabetes Mellitus, Type 2Islets of LangerhansKinesinsAnimalsFemaleGlucagonHumansInsulinInsulin-Secreting CellsInsulin SecretionMaleMiceMice, Inbred C57BLGlucagonInsulinKIF21A protein, humanKinesinsGlucagonInsulinMicrotubule (MT)Molecular motorPancreasSecretionSomatostatinType-2 diabetes (T2D)α-cellsβ-cellsδ-cells

Identifiers

PMID42336059
PMCPMC13351690

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