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Pericentrin Is Related to Abnormal β-Cell Insulin Secretion through F-Actin Regulation in Mice.

Zu Y, Gong Y, Wan L, Lv Y, Cui S, Jin X, Li C, Chen X - PLoS ONE (2015)

Bottom Line: The results revealed that PCNT expression in glucose-stimulated MIN6 cells reduced linearly with cytoplasmic insulin levels.The ERK inhibitor affected PCNT expression and F-actin expression linearly.The abnormal insulin secretion observed both in vivo and in vitro was associated with decreased PCNT expression, and F-actin was found to be the target of PCNT regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Geriatric Endocrinology, Chinese People's Liberation Army General Hospital, Beijing, 100853, China.

ABSTRACT
The aim of this study was to investigate the regulating effect of pericentrin (PCNT) on insulin secretion in the development of insulin resistance and to determine the underlying mechanism. PCNT expression was studied in different tissues of C57/B6 mice by reverse transcriptase-PCR and immunofluorescence. PCNT was highly expressed in organs involved in the regulation of metabolism, while cytoplasmic expression was only enriched in islet cells. PCNT expression was significantly lower in the central regions of insulin resistance (IR) mouse islets than in those of control mouse islets. PCNT expression was further studied in mouse MIN6 cells exposed to glucose stimulation, small interfering RNA (siRNA) against PCNT, and an ERK inhibitor (PD98095). The results revealed that PCNT expression in glucose-stimulated MIN6 cells reduced linearly with cytoplasmic insulin levels. MIN6 cells transfected with PCNT siRNA showed significantly decreased intracellular insulin and F-actin expression. The change in F-actin expression in MIN6 cells during PCNT siRNA interference showed a linear relationship with PCNT expression at different time points. The ERK inhibitor affected PCNT expression and F-actin expression linearly. The abnormal insulin secretion observed both in vivo and in vitro was associated with decreased PCNT expression, and F-actin was found to be the target of PCNT regulation.

No MeSH data available.


Related in: MedlinePlus

Comparison of PCNT expression in islets of IR and control mice.(A) IHC and (B) IF analysis of PCNT expression in the islets of IR and control mice. PCNT expression was significantly lower in the central region of islets in IR mice compared to those in the controls. (C) IHC staining for insulin, glycogen, and somatostatin expression in mouse islet cells. Beta cells showing robust insulin expression were centrally located in the islets and represented the majority of islet cells. Alpha cells expressed glucagon on the plasma membrane, and delta cells expressed cytoplasmic somatostatin and surrounded the islets.
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pone.0130458.g002: Comparison of PCNT expression in islets of IR and control mice.(A) IHC and (B) IF analysis of PCNT expression in the islets of IR and control mice. PCNT expression was significantly lower in the central region of islets in IR mice compared to those in the controls. (C) IHC staining for insulin, glycogen, and somatostatin expression in mouse islet cells. Beta cells showing robust insulin expression were centrally located in the islets and represented the majority of islet cells. Alpha cells expressed glucagon on the plasma membrane, and delta cells expressed cytoplasmic somatostatin and surrounded the islets.

Mentions: Insulin resistant models in C57BL/6 mice were developed by feeding mice a high-fat diet for 12 weeks. Glucose tolerance tests showed that plasma glucose levels and the area under the glucose level-time curves were significantly higher in the IR group than in the control group. At week 12, HOMA-IR values of mice in the IR group were significantly higher compared to those in the controls (1.39 ± 0.14 vs. 0.44 ± 0.01, P < 0.01). IHC and IF results showed that PCNT expression was significantly decreased in IR mouse pancreatic tissue, mainly in the central part of the islets (Fig 2A and 2B). Insulin, glycogen, and somatostatin were stained in the islets cells (Fig 2C). Beta cells showing robust insulin expression were centrally located. This revealed that PCNT expression in central mouse islets might locate in beta cells. Moreover, the reduction in PCNT expression in central islets was not related to beta cell number, because the traditional proliferation indices (CyclinD2 and CDK4) were increased in western blot (Fig 2D).


Pericentrin Is Related to Abnormal β-Cell Insulin Secretion through F-Actin Regulation in Mice.

Zu Y, Gong Y, Wan L, Lv Y, Cui S, Jin X, Li C, Chen X - PLoS ONE (2015)

Comparison of PCNT expression in islets of IR and control mice.(A) IHC and (B) IF analysis of PCNT expression in the islets of IR and control mice. PCNT expression was significantly lower in the central region of islets in IR mice compared to those in the controls. (C) IHC staining for insulin, glycogen, and somatostatin expression in mouse islet cells. Beta cells showing robust insulin expression were centrally located in the islets and represented the majority of islet cells. Alpha cells expressed glucagon on the plasma membrane, and delta cells expressed cytoplasmic somatostatin and surrounded the islets.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4470688&req=5

pone.0130458.g002: Comparison of PCNT expression in islets of IR and control mice.(A) IHC and (B) IF analysis of PCNT expression in the islets of IR and control mice. PCNT expression was significantly lower in the central region of islets in IR mice compared to those in the controls. (C) IHC staining for insulin, glycogen, and somatostatin expression in mouse islet cells. Beta cells showing robust insulin expression were centrally located in the islets and represented the majority of islet cells. Alpha cells expressed glucagon on the plasma membrane, and delta cells expressed cytoplasmic somatostatin and surrounded the islets.
Mentions: Insulin resistant models in C57BL/6 mice were developed by feeding mice a high-fat diet for 12 weeks. Glucose tolerance tests showed that plasma glucose levels and the area under the glucose level-time curves were significantly higher in the IR group than in the control group. At week 12, HOMA-IR values of mice in the IR group were significantly higher compared to those in the controls (1.39 ± 0.14 vs. 0.44 ± 0.01, P < 0.01). IHC and IF results showed that PCNT expression was significantly decreased in IR mouse pancreatic tissue, mainly in the central part of the islets (Fig 2A and 2B). Insulin, glycogen, and somatostatin were stained in the islets cells (Fig 2C). Beta cells showing robust insulin expression were centrally located. This revealed that PCNT expression in central mouse islets might locate in beta cells. Moreover, the reduction in PCNT expression in central islets was not related to beta cell number, because the traditional proliferation indices (CyclinD2 and CDK4) were increased in western blot (Fig 2D).

Bottom Line: The results revealed that PCNT expression in glucose-stimulated MIN6 cells reduced linearly with cytoplasmic insulin levels.The ERK inhibitor affected PCNT expression and F-actin expression linearly.The abnormal insulin secretion observed both in vivo and in vitro was associated with decreased PCNT expression, and F-actin was found to be the target of PCNT regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Geriatric Endocrinology, Chinese People's Liberation Army General Hospital, Beijing, 100853, China.

ABSTRACT
The aim of this study was to investigate the regulating effect of pericentrin (PCNT) on insulin secretion in the development of insulin resistance and to determine the underlying mechanism. PCNT expression was studied in different tissues of C57/B6 mice by reverse transcriptase-PCR and immunofluorescence. PCNT was highly expressed in organs involved in the regulation of metabolism, while cytoplasmic expression was only enriched in islet cells. PCNT expression was significantly lower in the central regions of insulin resistance (IR) mouse islets than in those of control mouse islets. PCNT expression was further studied in mouse MIN6 cells exposed to glucose stimulation, small interfering RNA (siRNA) against PCNT, and an ERK inhibitor (PD98095). The results revealed that PCNT expression in glucose-stimulated MIN6 cells reduced linearly with cytoplasmic insulin levels. MIN6 cells transfected with PCNT siRNA showed significantly decreased intracellular insulin and F-actin expression. The change in F-actin expression in MIN6 cells during PCNT siRNA interference showed a linear relationship with PCNT expression at different time points. The ERK inhibitor affected PCNT expression and F-actin expression linearly. The abnormal insulin secretion observed both in vivo and in vitro was associated with decreased PCNT expression, and F-actin was found to be the target of PCNT regulation.

No MeSH data available.


Related in: MedlinePlus