eNOS-defi cient mice were shown to develop hypertension and insulin resistance either in basal conditions (eNOS null) or upon high fat diet, HFD (eNOS +/- heterozygotes). In the model of HFD-fed eNOS +/- mice, we investigated putative pancreatic morphological changes to fi nd out clues of the cellular mechanisms responsible for their compensatory hyperinsulinemic response. C57BL6 wild type (WT) and eNOS +/- mice were fed with either chow or HFD for 16 weeks. A group of chow-fed eNOS null mice was also studied. Basal blood glucose and insulin were monitored and glucose and insulin tolerance tests performed. Then mice were sacrifi ced and fragments of pancreas were routinely processed for histological, immunohistochemical and ultrastructural observation (with suitable image analysis). Both WT and eNOS +/- mice fed with HFD developed insulin resistance, as assessed by fasting hyperglycemia with hyperinsulinemia, glucose intolerance and reduced response to exogenous insulin. In HFDfed groups, evidence of compensatory adaptation of -cells was provided by increased total pancreatic insulin content, larger -cell fractional area and enhanced number of extra-islet -cell clusters (2-5 cells) as compared to chow-fed groups. At ultrastructural level, in the HFD-fed eNOS +/- group only, besides single -cells surrounded by exocrine cells, a number of cells simultaneously containing zymogen and insulin granules were surprisingly observed in most pancreases examined. Such cells, usually retaining the extended and thick endoplasmic reticulum typical of acinar cells, represent an interesting example of direct exocrine/-cell trans-differentiation, likely triggered by strong insulin-demanding metabolic stress, yet independent on damaging stimuli, such as duct ligation as reported in literature. The reason why such trans-differentiation process was only detected in the eNOS +/- mice fed with HFD remains an interesting matter of future investigation.

Beta-cell hyperplasia and direct acinar-beta-cell trans-differentiation in insulin-resistant partially eNOS-deficient mice.

MASINI, MATILDE;NOVELLI, MICHELA;CAMPANI, DANIELA;MASIELLO, PELLEGRINO
2014-01-01

Abstract

eNOS-defi cient mice were shown to develop hypertension and insulin resistance either in basal conditions (eNOS null) or upon high fat diet, HFD (eNOS +/- heterozygotes). In the model of HFD-fed eNOS +/- mice, we investigated putative pancreatic morphological changes to fi nd out clues of the cellular mechanisms responsible for their compensatory hyperinsulinemic response. C57BL6 wild type (WT) and eNOS +/- mice were fed with either chow or HFD for 16 weeks. A group of chow-fed eNOS null mice was also studied. Basal blood glucose and insulin were monitored and glucose and insulin tolerance tests performed. Then mice were sacrifi ced and fragments of pancreas were routinely processed for histological, immunohistochemical and ultrastructural observation (with suitable image analysis). Both WT and eNOS +/- mice fed with HFD developed insulin resistance, as assessed by fasting hyperglycemia with hyperinsulinemia, glucose intolerance and reduced response to exogenous insulin. In HFDfed groups, evidence of compensatory adaptation of -cells was provided by increased total pancreatic insulin content, larger -cell fractional area and enhanced number of extra-islet -cell clusters (2-5 cells) as compared to chow-fed groups. At ultrastructural level, in the HFD-fed eNOS +/- group only, besides single -cells surrounded by exocrine cells, a number of cells simultaneously containing zymogen and insulin granules were surprisingly observed in most pancreases examined. Such cells, usually retaining the extended and thick endoplasmic reticulum typical of acinar cells, represent an interesting example of direct exocrine/-cell trans-differentiation, likely triggered by strong insulin-demanding metabolic stress, yet independent on damaging stimuli, such as duct ligation as reported in literature. The reason why such trans-differentiation process was only detected in the eNOS +/- mice fed with HFD remains an interesting matter of future investigation.
2014
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/749686
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