AULA 18

Mecanismos moleculares do controle de GLUCOSE 1. sinalizao pela insulina 2. as cinases mTOR e AKT 3. efeito da amilina e de integrinas 4. a regulao dos niveis de glucagon 5. mecanismos na diabetes tipo 1 e tipo 2

mTOR = mammalian target of rapamycin uma protena cinase de serina /treonina

mTOR

Regula : crescimento celular proliferao sntese proteica transcrio Pertence familia das cinases de fosfatidil-inositol

mTOR

mTOR complexo 1: constituido pela protena mTOR + uma protena reguladora + protena G + PRAS40 + DETOR Complexo funciona como sensor de estado alimentar, energtico e de equilibrio redox A atividade do complexo estimulada pela insulin, pelo stress oxidativo e outros modeladores.

mTOR

Hepatic mTORC2 Activates Glycolysis and Lipogenesis through Akt, Glucokinase, and SREBP1c

Cell Metabolism, Volume 15, Issue 5, 725-738, 19 April 2012 Asami Hagiwara, Marion Cornu, Nadine Cybulski, Pazit Polak, Charles Betz, Francesca Trapani, Luigi Terracciano, Markus H. Heim, Markus A. Regg, Michael N. H

A amilina um peptdeo com 37 aminocidos que secretado pelas clulas beta do pncreas junto com a insulina (numa proporo de 100:1).

Regulation of Glucagon Secretion 1. Low blood sugar levels or hypoglycemia induce glucagon secretion. 2. high blood sugar levels inhibit it. 3. High amino acid levels in the blood following a protein-rich meal promote secretion of this hormone. 4. Exercise also appears to promote glucagon secretion 5. the hormones insulin and somatostatin inhibit it.

FIGURE 1 | Endocrine and neuroendocrine regulation of postprandial glucose homeostasis.

Darleen A. Sandoval, Silvana Obici & Randy J. Seeley (2009) Targeting the CNS to treat type 2 diabetes Nature Reviews Drug Discovery 8, 386-398

FIGURE 2 | Central nervous system (CNS) regulation of glucose homeostasis.

FIGURE 3 | Neuronal fuel sensing and regulation of energy and glucose homeostasis.

FIGURE 4 | Potential integration of hypothalamic insulin and leptin signalling on mTOR and AMPK and how this might regulate glucose homeostasis.

G protein-coupled receptors for energy metabolites as new therapeutic targets Clara C. Blad, Cong Tang & Stefan Offermanns Nature Reviews Drug Discovery 11, 603-619 (August 2012)

Armanda Passos