Hypoglycemia Reduces Vascular Endothelial Growth Factor A Production by Pancreatic Beta Cells as a Regulator of Beta Cell Mass

Xiao, Xianmin; Guo, Ping; Chen, Zean; El-Gohary, Yousef; Wiersch, John; Gaffar, Iljana; Prasadan, Krishna; Chiyo, Shiota; Gittes, George K.

doi:10.1074/jbc.m112.422949

Cited by 83 publications

(110 citation statements)

References 43 publications

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“…Purity of sorted cell factions was evaluated by analysis of expression of cell-type specific markers with RT-qPCR. Beta cell isolation from MIP-GFP mice has been described previously (46).…”

Section: Methodsmentioning

confidence: 99%

“…RNA Isolation and RT-qPCR-RNA extraction and RT-qPCR have been described previously (8,45,46). Primers were all purchased from Qiagen.…”

Section: Methodsmentioning

confidence: 99%

“…Pancreatic Digestion and FACS-Pancreatic duct perfusion and subsequent digestion of the pancreas was performed as described previously (45,46). Pancreatic digests were either incubated with Fluorescein Dolichos Biflorus Agglutinin (DBA, Vector Lab, a duct-binding lectin) for 30 min to allow isolation of green DBA ϩ duct cells by FACS, or else for Ngn3-Cre; mTmG pancreas sequentially incubated with biotin-DBA (Vector Lab) and streptavidin-cy5 for 30 min to allow isolation of mG ϩ duct cells and mG Ϫ duct cells by FACS.…”

Section: Methodsmentioning

confidence: 99%

“…Nuclear staining is performed with Hoechst solution (BD). Imaging of cryosections is performed as described previously (8,(45)(46)(47).…”

Section: Methodsmentioning

confidence: 99%

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Neurogenin3 Activation Is Not Sufficient to Direct Duct-to-Beta Cell Transdifferentiation in the Adult Pancreas

Xiao

Guo

Shiota

et al. 2013

Journal of Biological Chemistry

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Background: Whether neurogenin3 activation represents beta cell neogenesis in adults is controversial. Results: Neurogenin3-activated pancreatic duct cells do not become beta cells. Conclusion: Neurogenin3 activation is not a signature for adult beta cell neogenesis. Significance: Our data strongly argue against the widely held belief that neurogenin3 is a marker of beta cell neogenesis in the adult pancreas, especially from duct cells.

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Section: Methodsmentioning

confidence: 99%

“…RNA Isolation and RT-qPCR-RNA extraction and RT-qPCR have been described previously (8,45,46). Primers were all purchased from Qiagen.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Nuclear staining is performed with Hoechst solution (BD). Imaging of cryosections is performed as described previously (8,(45)(46)(47).…”

Section: Methodsmentioning

confidence: 99%

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Neurogenin3 Activation Is Not Sufficient to Direct Duct-to-Beta Cell Transdifferentiation in the Adult Pancreas

Xiao

Guo

Shiota

et al. 2013

Journal of Biological Chemistry

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“…In theory, a proper PDL should not affect major pancreatic vessels and should not cause significant tissue necrosis. The exocrine tissue within the ligated tail of the pancreas undergoes severe inflammation, with essentially complete loss of acinar tissue ( Figure 6, A-C) (37,38). Therefore, the ligated tail of the PDL pancreas becomes more translucent (see also Figure 1B) within 1 week after PDL due to exocrine atrophy.…”

Section: Introductionmentioning

confidence: 99%

No evidence for β cell neogenesis in murine adult pancreas

Xiao¹,

Chen²,

Shiota³

et al. 2013

J. Clin. Invest.

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Whether facultative β cell progenitors exist in the adult pancreas is a major unsolved question. To date, lineage-tracing studies have provided conflicting results. To track β cell neogenesis in vivo, we generated transgenic mice that transiently coexpress mTomato and GFP in a time-sensitive, nonconditional Cre-mediated manner, so that insulin-producing cells express GFP under control of the insulin promoter, while all other cells express mTomato (INS Cre mTmG mice). Newly differentiated β cells were detected by flow cytometry and fluorescence microscopy, taking advantage of their transient coexpression of GFP and mTomato fluorescent proteins. We found that β cell neogenesis predominantly occurs during embryogenesis, decreases dramatically shortly after birth, and is completely absent in adults across various models of β cell loss, β cell growth and regeneration, and inflammation. Moreover, we demonstrated upregulation of neurogenin 3 (NGN3) in both proliferating ducts and preexisting β cells in the ligated pancreatic tail after pancreatic ductal ligation. These results are consistent with some recent reports, but argue against the widely held belief that NGN3 marks cells undergoing endocrine neogenesis in the pancreas. Our data suggest that β cell neogenesis in the adult pancreas occurs rarely, if ever, under either normal or pathological conditions.

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Database search of spontaneous reports and pharmacological investigations on the sulfonylureas and glinides‐induced atrophy in skeletal muscle

Mele

Calzolaro

Cannone

et al. 2014

Pharmacology Res & Perspec

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The ATP-sensitive K+ (KATP) channel is an emerging pathway in the skeletal muscle atrophy which is a comorbidity condition in diabetes. The “in vitro” effects of the sulfonylureas and glinides were evaluated on the protein content/muscle weight, fibers viability, mitochondrial succinic dehydrogenases (SDH) activity, and channel currents in oxidative soleus (SOL), glycolitic/oxidative flexor digitorum brevis (FDB), and glycolitic extensor digitorum longus (EDL) muscle fibers of mice using biochemical and cell-counting Kit-8 assay, image analysis, and patch-clamp techniques. The sulfonylureas were: tolbutamide, glibenclamide, and glimepiride; the glinides were: repaglinide and nateglinide. Food and Drug Administration-Adverse Effects Reporting System (FDA-AERS) database searching of atrophy-related signals associated with the use of these drugs in humans has been performed. The drugs after 24 h of incubation time reduced the protein content/muscle weight and fibers viability more effectively in FDB and SOL than in the EDL. The order of efficacy of the drugs in reducing the protein content in FDB was: repaglinide (EC50 = 5.21 × 10−6) ≥ glibenclamide(EC50 = 8.84 × 10−6) > glimepiride(EC50 = 2.93 × 10−5) > tolbutamide(EC50 = 1.07 × 10−4) > nateglinide(EC50 = 1.61 × 10−4) and it was: repaglinide(7.15 × 10−5) ≥ glibenclamide(EC50 = 9.10 × 10−5) > nateglinide(EC50 = 1.80 × 10−4) ≥ tolbutamide(EC50 = 2.19 × 10−4) > glimepiride(EC50=–) in SOL. The drug-induced atrophy can be explained by the KATP channel block and by the enhancement of the mitochondrial SDH activity. In an 8-month period, muscle atrophy was found in 0.27% of the glibenclamide reports in humans and in 0.022% of the other not sulfonylureas and glinides drugs. No reports of atrophy were found for the other sulfonylureas and glinides in the FDA-AERS. Glibenclamide induces atrophy in animal experiments and in human patients. Glimepiride shows less potential for inducing atrophy.

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Hypoglycemia Reduces Vascular Endothelial Growth Factor A Production by Pancreatic Beta Cells as a Regulator of Beta Cell Mass

Cited by 83 publications

References 43 publications

Neurogenin3 Activation Is Not Sufficient to Direct Duct-to-Beta Cell Transdifferentiation in the Adult Pancreas

Neurogenin3 Activation Is Not Sufficient to Direct Duct-to-Beta Cell Transdifferentiation in the Adult Pancreas

No evidence for β cell neogenesis in murine adult pancreas

Database search of spontaneous reports and pharmacological investigations on the sulfonylureas and glinides‐induced atrophy in skeletal muscle

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