from sympathetic innervation and epinephrine from the ) can reinforce the actions of glucagon. Adipocytes also express the glucagon receptor, as well as the β2-and β3-adrenergic receptors that respond to catecholamines in response to hypoglycemia, exertion, or certain stresses. Skeletal muscle is not a target of glucagon but does respond to catecholamines stimulation through β2-adrenergic receptors. Skeletal muscle is very responsive to intracellular Ca++ , which increases during physical exertion/movement, and to an increase in the intracellular adenosine monophosphate (AMP):ATP ratio, which activates AMP kinase.
Finally, it is important to understand that the pathways upregulated during the fasting phase are opposed by insulin-dependent pathways that are most active during the digestive phase (discussed later). Thus attenuation of insulin signaling also contributes to the ability of hepatocytes, skeletal myocytes, and adipocytes to display an integrated response to the metabolic challenges of the fasting phase.
•Fig. 39.5 TheisletsofLangerhans(endocrinepancreas)fromrat.A, Pancreashistologyshowingexocrineaciniwheredigestiveenzymesareproducedtobedeliveredtotheduodenumviathepancreaticduct,andanendocrineisletwhereinsulinandglucagonareproducedanddeliveredtothecirculationuponuptakebyarichcapillarybed.B, Stainingofendocrineisletforinsulinwithinbetacells;thesearethemostnumerouscelltypeandareprimarilylocatedcentrallywithintheislet.C, Stainingofendocrineisletforglucagonwithalphacells;thesearemuchlessnumerousthanbetacellsandareprimarilylocatedalongtheperipheryoftheislet.
•Fig. 39.6 ProinsulinisprocessedbyprohormoneconvertasesintoamatureinsulinmoleculewithtwopeptidestrandslinkedbyH-bondsandaCpeptide.Botharesecretedinequimolarratios.(FromWhiteBA,PorterfieldSP[eds].Endocrine and Reproductive Physiology. 4thed.Philadelphia:Mosby/Elsevier;2013.)C peptide C peptide Insulin B B Converting enzymes Proinsulin “folded” S-S bonds formed Endoplasmic reticulum Golgi Secretory granule A A S S S S S S S S S S S S
The islets of Langerhans constitute the endocrine pancreas (
Fig. 39.6 ). Approximately 1 million islets making up about 1% to 2% of the pancreatic mass are spread throughout the exocrine pancreas (see ). The islets are composed of several cell types, each producing a different hormone. Beta cells make up about three-fourths of the cells of the islets and produce the hormone insulin (see
Fig. 39.5B ). Alpha cells account for about 10% of islet cells and secrete glucagon (see
Fig. 39.5C ). Other endocrine cell types reside within islets, but their respective hormone products are of marginal or unclear importance and thus will not be discussed further.
Blood flow to the islets is somewhat autonomous from blood flow to the surrounding exocrine pancreatic tissue. Blood flow through the islets passes from beta cells, which predominate in the center of the islet, to alpha and delta cells, which predominate in the periphery (see
Fig.
38.5B-C ). Consequently the first cells affected by circulating insulin are the alpha cells, in which insulin inhibits glucagon secretion.