Metabolic crosstalk between fatty pancreas and fatty liver: effects on local inflammation and insulin secretion

Aims/hypothesis

Obesity-linked ectopic fat accumulation is associated with the development of type 2 diabetes. Whether pancreatic and liver steatosis impairs insulin secretion is controversial. We examined the crosstalk of human pancreatic fat cells with islets and the role of diabetogenic factors, i.e. palmitate and fetuin-A, a hepatokine released from fatty liver.

Methods

Human pancreatic resections were immunohistochemically stained for insulin, glucagon, somatostatin and the macrophage/monocyte marker CD68. Pancreatic adipocytes were identified by Oil Red O and adiponectin staining. Primary pancreatic pre-adipocytes and differentiated adipocytes were co-cultured with human islets isolated from organ donors and the metabolic crosstalk between fatty liver and fatty pancreas was mimicked by the addition of palmitate and fetuin-A. Insulin secretion was evaluated by ELISA and RIA. Cytokine expression and secretion were assessed by RT-PCR and multiplex assay, respectively. Subcellular distribution of proteins was examined by confocal microscopy and protein phosphorylation by western blotting.

Results

In human pancreatic parenchyma, highly differentiated adipocytes were detected in the proximity of islets with normal architecture and hormone distribution. Infiltration of adipocytes was associated with an increased number of CD68-positive cells within islets. In isolated primary pancreatic pre-adipocytes and differentiated adipocytes, palmitate and fetuin-A induced IL6, CXCL8 and CCL2 mRNA expression. Cytokine production was toll-like receptor 4 (TLR4)-dependent and further accentuated in pre-adipocytes when co-cultured with islets. In islets, IL6 and CXCL8 mRNA levels were also increased by fetuin-A and palmitate. Only in macrophages within the isolated islets, palmitate and fetuin-A stimulated the production of the cytotoxic cytokine IL-1β. Palmitate, but not fetuin-A, exerted pro-apoptotic effects in islet cells. Instead, fetuin-A impaired glucose-induced insulin secretion in a TLR4-independent, but c-Jun N-terminal kinase- and Ca²⁺-dependent, manner.

Conclusions/interpretation

These results provide the first evidence that fetuin-A-mediated metabolic crosstalk of fatty liver with islets may contribute to obesity-linked glucose blindness of beta cells, while fatty pancreas may exacerbate local inflammation.

     

Symptomatic pericardial cyst: a case series

Pericardial cysts are most commonly located at the cardiophrenic angle or, rarely, in the posterior or anterior superior mediastinum. The majority of pericardial cysts are asymptomatic and are found incidentally. Symptomatic pericardial cysts present with dyspnoea, chest pain, or persistent cough. We describe four patients with symptomatic pericardial cysts who were treated with either echocardiographically guided percutaneous aspiration or video-assisted thoracoscopic surgery, or both; thoracotomy; or conservative therapy.     

Clinical evaluation of brushing time and plaque removal potential of two manual toothbrushes

Abstract: Aim: To compare plaque removal efficacy of Oral‐B CrossAction (CA) used for 1 min with an American Dental Association (ADA) manual toothbrush used for 2 or 5 min in an examiner‐blind, three‐treatment, six‐period crossover study. Materials and methods: After refraining from all oral hygiene procedures for 23–25 h, subjects were randomly assigned to one of nine possible six‐period (visit) treatment sequences. Plaque was assessed at baseline (Rustogi Modified Navy Plaque Index). Post‐brushing scores were recorded after brushing with a marketed dentifrice and the assigned toothbrush for the specified duration. The same procedure was followed at each of six subsequent visits. Clinical measurements were carried out by the same examiner. Results: Forty subjects completed the study. All three treatments effectively removed plaque from the whole mouth, along the gingival margin and from approximal surfaces. Whole mouth and gingival margin plaque removal scores with CA for 1 min did not differ significantly from scores with the ADA toothbrush used for 2 min. The ADA brush used for 5 min showed significantly greater whole mouth (P < 0.001) and gingival margin (P < 0.001) plaque reduction than the two other treatments. Approximal plaque removal scores did not differ between the three treatments. Conclusions: Efficient plaque removal can be achieved after 1 min of brushing with CA. The amount of plaque removed did not differ significantly from that achieved with the ADA brush after 2 min of brushing. Greater whole mouth and gingival margin plaque removal scores were seen with the ADA brush after 5 min.