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Vascularization of human islets by adaptable endothelium for durable and functional subcutaneous engraftment.
Sci Adv
January 2025
Division of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Tissue-specific endothelial cells (ECs) are critical for the homeostasis of pancreatic islets and most other tissues. In vitro recapitulation of islet biology and therapeutic islet transplantation both require adequate vascularization, which remains a challenge. Using human reprogrammed vascular ECs (R-VECs), human islets were functionally vascularized in vitro, demonstrating responsive, dynamic glucose-stimulated insulin secretion and Ca influx.
View Article and Find Full Text PDFNutritional state-dependent modulation of insulin-producing cells in .
Elife
January 2025
Neurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, Julius-Maximilians-University of Würzburg, Würzburg, Germany.
Insulin plays a key role in metabolic homeostasis. insulin-producing cells (IPCs) are functional analogues of mammalian pancreatic beta cells and release insulin directly into circulation. To investigate the in vivo dynamics of IPC activity, we quantified the effects of nutritional and internal state changes on IPCs using electrophysiological recordings.
View Article and Find Full Text PDFSynthetic studies of the mutant proinsulin syndrome demonstrate correlation between folding efficiency and age of diabetes onset.
Int J Pept Res Ther
January 2025
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States 46202.
Purpose: Heterozygous mutations in the insulin gene can give rise to a monogenic diabetes syndrome due to toxic misfolding of the variant proinsulin in the endoplasmic reticulum (ER) of pancreatic β-cells. Clinical mutations are widely distributed in the sequence (86 amino acids). Misfolding induces chronic ER stress and interferes in with wildtype biosynthesis and secretion.
View Article and Find Full Text PDFDetection of Insulin in Insulin-Deficient Islets of Patients with Type 1 Diabetes.
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Laboratory of Nervous System Development, Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", Tsurupi Street, 3, 117418 Moscow, Russia.
Type 1 diabetes (T1D) is related to the autoimmune destruction of β-cells, leading to their almost complete absence in patients with longstanding T1D. However, endogenous insulin secretion persists in such patients as evidenced by the measurement of plasma C-peptide. Recently, a low level of insulin has been found in non-β islet cells of patients with longstanding T1D, indicating that other islet cell types may contribute to persistent insulin secretion.
View Article and Find Full Text PDFInsulin Receptor Substrate-2 Regulates the Secretion of Growth Factors in Response to Amino Acid Deprivation.
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January 2025
Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
Insulin receptor substrates (IRSs) are well-known mediators of the insulin and insulin-like growth factor (IGF)-I signaling pathways. We previously reported that the protein levels of IRS-2, a molecular species of IRS, were upregulated in the livers of rats fed a protein-restricted diet. This study aimed to elucidate the physiological role of IRS-2, whose level increases in response to protein restriction in cultured hepatocyte models.
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