Sympathetic innervation and epinephrine from the adrenal medulla can enhance the effects of glucagon. Glucagon receptor and β2- and β3-adrenergic receptors are also present in adipocytes, which respond to catecholamines during hypoglycemia, exertion, or certain stresses. Although skeletal muscle is not a direct target of glucagon, it does respond to catecholamines through β2-adrenergic receptors. Skeletal muscle is highly sensitive to intracellular Ca++ levels, which rise during physical activity, and to an increase in the intracellular AMP:ATP ratio, which activates AMP kinase.
It is worth noting that the pathways that are upregulated during fasting are counteracted by insulin-dependent pathways that are most active during digestion. Thus, the attenuation of insulin signaling also contributes to the coordinated response of hepatocytes, skeletal myocytes, and adipocytes to the metabolic challenges encountered during the fasting phase.
The endocrine pancreas, consisting of the islets of Langerhans, can be seen in Figure 39.5. These islets, which represent approximately 1% to 2% of the pancreatic mass and number around 1 million, are scattered throughout the exocrine pancreas. Different cell types within the islets produce various hormones. Beta cells, comprising approximately three-fourths of the islet cells, synthesize insulin (Figure 39.5B). Alpha cells, accounting for about 10% of the islet cells, secrete glucagon (Figure 39.5C). While other endocrine cell types also reside in the islets, the significance of their respective hormone products is uncertain and will not be further discussed.
Blood flow to the islets is somewhat independent of blood flow to the surrounding exocrine pancreatic tissue. Within the islets, blood flow moves from the beta cells, predominantly located in the center, to the alpha and delta cells, which are mainly situated in the periphery (Figure 38.5B-C). Consequently, circulating insulin primarily affects alpha cells, where it inhibits glucagon secretion.
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.