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1.
J Physiol ; 596(2): 197-215, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-28975620

RESUMO

KEY POINTS: We used a mouse expressing a light-sensitive ion channel in ß-cells to understand how α-cell activity is regulated by ß-cells. Light activation of ß-cells triggered a suppression of α-cell activity via gap junction-dependent activation of δ-cells. Mathematical modelling of human islets suggests that 23% of the inhibitory effect of glucose on glucagon secretion is mediated by ß-cells via gap junction-dependent activation of δ-cells/somatostatin secretion. ABSTRACT: Glucagon, the body's principal hyperglycaemic hormone, is released from α-cells of the pancreatic islet. Secretion of this hormone is dysregulated in type 2 diabetes mellitus but the mechanisms controlling secretion are not well understood. Regulation of glucagon secretion by factors secreted by neighbouring ß- and δ-cells (paracrine regulation) have been proposed to be important. In this study, we explored the importance of paracrine regulation by using an optogenetic strategy. Specific light-induced activation of ß-cells in mouse islets expressing the light-gated channelrhodopsin-2 resulted in stimulation of electrical activity in δ-cells but suppression of α-cell activity. Activation of the δ-cells was rapid and sensitive to the gap junction inhibitor carbenoxolone, whereas the effect on electrical activity in α-cells was blocked by CYN 154806, an antagonist of the somatostatin-2 receptor. These observations indicate that optogenetic activation of the ß-cells propagates to the δ-cells via gap junctions, and the consequential stimulation of somatostatin secretion inhibits α-cell electrical activity by a paracrine mechanism. To explore whether this pathway is important for regulating α-cell activity and glucagon secretion in human islets, we constructed computational models of human islets. These models had detailed architectures based on human islets and consisted of a collection of >500 α-, ß- and δ-cells. Simulations of these models revealed that this gap junctional/paracrine mechanism accounts for up to 23% of the suppression of glucagon secretion by high glucose.


Assuntos
Simulação por Computador , Junções Comunicantes/fisiologia , Células Secretoras de Glucagon/fisiologia , Células Secretoras de Insulina/fisiologia , Células Secretoras de Somatostatina/fisiologia , Animais , Cálcio/metabolismo , Comunicação Celular , Células Cultivadas , Feminino , Células Secretoras de Glucagon/citologia , Células Secretoras de Glucagon/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Somatostatina/metabolismo , Células Secretoras de Somatostatina/citologia , Células Secretoras de Somatostatina/metabolismo
2.
IEEE Trans Image Process ; 7(11): 1609-15, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-18276226

RESUMO

This work presents a new approach and an algorithm for binary image representation, which is applied for the fast and efficient computation of moments on binary images. This binary image representation scheme is called image block representation, since it represents the image as a set of nonoverlapping rectangular areas. The main purpose of the image block representation process is to provide an efficient binary image representation rather than the compression of the image. The block represented binary image is well suited for fast implementation of various processing and analysis algorithms in a digital computing machine. The two-dimensional (2-D) statistical moments of the image may be used for image processing and analysis applications. A number of powerful shape analysis methods based on statistical moments have been presented, but they suffer from the drawback of high computational cost. The real-time computation of moments in block represented images is achieved by exploiting the rectangular structure of the blocks.

3.
ISRN Surg ; 2011: 529876, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22084764

RESUMO

Background and Aims. Intraperitoneal chemotherapy is a basic tool in the treatment of peritoneal malignancy. The purpose of the study is to investigate the effect of adjuvant perioperative intraperitoneal chemotherapy in the treatment of locally advanced colorectal cancer. Patients and Methods. Patients with T(3) and T(4) colorectal carcinomas that underwent R(0) resection received either hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC group = 40 patients) or early postoperative intraperitoneal chemotherapy (EPIC group = 67 patients). The survival, the recurrences and the sites of recurrence were assessed. Results. The 3-year survival rate for HIPEC group was 100% and for EPIC group 69% (P = .011). Nodal infiltration was found to be the single prognostic indicator of survival. The incidence of recurrence in EPIC group was higher than in HIPEC group (P = .009). The independent indicators of recurrence were the use of HIPEC and the degree of differentiation (P < .05). Conclusions. Intraperitoneal chemotherapy, particularly HIPEC, as an adjuvant in locally advanced colorectal carcinomas appears to improve survival and decrease the incidence of recurrence.

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