The Endocrine Pancreas Regulation of Carbohydrate Metabolism
Pancreatic Anatomy Gland with both exocrine and endocrine functions15-25 cm long60-100 gLocation: retro-peritoneum, 2nd lumbar vertebral levelExtends in an oblique, transverse positionParts of pancreas: head, neck, body and tail
Head of Pancreas Includes uncinate processFlattened structure, 2 â 3 cm thickAttached to the 2nd and 3rd portions of duodenum on the rightEmerges into neck on the leftBorder b/w head and neck is determined by GDA insertionSPDA and IPDA anastamose between the duodenum and the right lateral border
Neck of Pancreas 2.5 cm in lengthStraddles SMV and PVAntero-superior surface supports the pylorusSuperior mesenteric vessels emerge from the inferior borderPosteriorly, SMV and splenic vein confluence to form portal veinPosteriorly, mostly no branches to pancreas
Body of Pancreas Elongated, long structureAnterior surface, separated from stomach by lesser sacPosterior surface, related to aorta, lt. adrenal gland, lt. renal vessels and upper 1/3rd of lt. kidneySplenic vein runs embedded in the post. SurfaceInferior surface is covered by transverse mesocolon
Tail of Pancreas Narrow, short segmentLies at the level of the 12th thoracic vertebraEnds within the splenic hilumLies in the splenophrenic ligamentAnteriorly, related to splenic flexure of colonMay be injured during splenectomy (fistula)
Pancreatic Duct Main duct (Wirsung) runs the entire length of pancreasJoins CBD at the ampulla of Vater2 â 4 mm in diameter, 20 secondary branchesDuctal pressure is 15 â 30 mm Hg (vs. 7 â 17 in CBD) thus preventing damage to panc. ductLesser duct (Santorini) drains superior portion of head and empties separately into 2nd portion of duodenum
Arterial Supply of Pancreas Variety of major arterial sources (celiac, SMA and splenic)Celiac ï Common Hepatic Artery ï Gastroduodenal Artery ï Superior pancreaticoduodenal artery which divides into anterior and posterior branchesSMA ï Inferior pancreaticoduodenal artery which divides into anterior and posterior branches
Arterial Supply of Pancreas Anterior collateral arcade between anterosuperior and anteroinferior PDA Posterior collateral arcade between posterosuperior and posteroinferior PDABody and tail supplied by splenic artery by about 10 branchesThree biggest branches areDorsal pancreatic arteryPancreatica Magna (midportion of body)Caudal pancreatic artery (tail)
Pancreatic Arterial Supply
Venous Drainage of Pancreas Follows arterial supplyAnterior and posterior arcades drain head and the bodySplenic vein drains the body and tailMajor drainage areas areSuprapancreatic PVRetropancreatic PVSplenic veinInfrapancreatic SMVUltimately, into portal vein
Venous Drainage of the Pancreas
Lymphatic Drainage Rich periacinar network that drain into 5 nodal groupsSuperior nodesAnterior nodesInferior nodesPosterior PD nodesSplenic nodes
Innervation of Pancreas Sympathetic fibers from the splanchnic nervesParasympathetic fibers from the vagusBoth give rise to intrapancreatic periacinar plexusesParasympathetic fibers stimulate both exocrine and endocrine secretionSympathetic fibers have a predominantly inhibitory effect
Innervation of Pancreas Peptidergic neurons that secrete amines and peptides (somatostatin, vasoactive intestinal peptide, calcitonin gene-related peptide, and galaninRich afferent sensory fiber networkGanglionectomy or celiac ganglion blockade interrupt these somatic fibers (pancreatic pain)
Pancreatic Hormones, Insulin and Glucagon, Regulate Metabolism
Production of Pancreatic Hormones by Three Cell Types Alpha cells produce glucagon.Beta cells produce insulin.Delta cells produce somatostatin.
Islet of Langerhans Cross-section Three cell types are present, A (glucagon secretion), B (Insulin secretion) and D (Somatostatin secretion)A and D cells are located around the perimeter while B cells are located in the interiorVenous return containing insulin flows by the A cells on its way out of the islets
Pancreatic Hormones, Insulin and Glucagon, Regulate Metabolism Figure 22-8: Metabolism is controlled by insulin and glucagon
Structure of Insulin Insulin is a polypeptide hormone, composed of two chains (A and B)BOTH chains are derived from proinsulin, a prohormone.The two chains are joined by disulfide bonds.
Roles of Insulin Acts on tissues (especially liver, skeletal muscle, adipose) to increase uptake of glucose and amino acids.- without insulin, most tissues do not take in glucose and amino acids well (except brain).Increases glycogen production (glucose storage) in the liver and muscle.Stimulates lipid synthesis from free fatty acids and triglycerides in adipose tissue.Also stimulates potassium uptake by cells (role in potassium homeostasis).
The Insulin Receptor The insulin receptor is composed of two subunits, and has intrinsic tyrosine kinase activity.Activation of the receptor results in a cascade of phosphorylation events:
Specific Targets of Insulin Action: Carbohydrates Activation of glycogen synthetase. Converts glucose to glycogen.Inhibition of phosphoenolpyruvate carboxykinase. Inhibits gluconeogenesis. Increased activity of glucose transporters. Moves glucose into cells.
Specific Targets of Insulin Action: Lipids Activation of acetyl CoA carboxylase. Stimulates production of free fatty acids from acetyl CoA.Activation of lipoprotein lipase (increases breakdown of triacylglycerol in the circulation). Fatty acids are then taken up by adipocytes, and triacylglycerol is made and stored in the cell.
Regulation of Insulin Release Major stimulus: increased blood glucose levels- after a meal, blood glucose increases - in response to increased glucose, insulin is released - insulin causes uptake of glucose into tissues, so blood glucose levels decrease.- insulin levels decline as blood glucose declines
Insulin Action on Cells: Dominates in Fed State Metabolism ï glucose uptake in most cells(not active muscle)ï glucose use and storageï protein synthesisï fat synthesis
Insulin Action on Cells: Dominates in Fed State Metabolism
Insulin: Summary and Control Reflex Loop
Other Factors Regulating Insulin Release Amino acids stimulate insulin release (increased uptake into cells, increased protein synthesis).Keto acids stimulate insulin release (increased glucose uptake to prevent lipid and protein utilization).Insulin release is inhibited by stress-induced increase in adrenal epinephrine- epinephrine binds to alpha adrenergic receptors on beta cells - maintains blood glucose levelsGlucagon stimulates insulin secretion (glucagon has opposite actions).
Structure and Actions of Glucagon Peptide hormone, 29 amino acidsActs on the liver to cause breakdown of glycogen (glycogenolysis), releasing glucose into the bloodstream.Inhibits glycolysisIncreases production of glucose from amino acids (gluconeogenesis).Also increases lipolysis, to free fatty acids for metabolism.Result: maintenance of blood glucose levels during fasting.
Mechanism of Action of Glucagon Main target tissues: liver, muscle, and adipose tissueBinds to a Gs-coupled receptor, resulting in increased cyclic AMP and increased PKA activity.Also activates IP3 pathway (increasing Ca++)
Glucagon prevents hypoglycemia by ï cell production of glucoseLiver is primary target to maintain blood glucose levels Glucagon Action on Cells: Dominates in Fasting State Metabolism
Glucagon Action on Cells: Dominates in Fasting State Metabolism
Targets of Glucagon Action Activates a phosphorylase, which cleaves off a glucose 1-phosphate molecule off of glycogen.Inactivates glycogen synthase by phosphorylation (less glycogen synthesis).Increases phosphoenolpyruvate carboxykinase, stimulating gluconeogenesisActivates lipases, breaking down triglycerides.Inhibits acetyl CoA carboxylase, decreasing free fatty acid formation from acetyl CoAResult: more production of glucose and substrates for metabolism
Regulation of Glucagon Release Increased blood glucose levels inhibit glucagon release.Amino acids stimulate glucagon release (high protein, low carbohydrate meal).Stress: epinephrine acts on beta-adrenergic receptors on alpha cells, increasing glucagon release (increases availability of glucose for energy).Insulin inhibits glucagon secretion.
Other Factors Regulating Glucose Homeostasis Glucocorticoids (cortisol): stimulate gluconeogenesis and lipolysis, and increase breakdown of proteins.Epinephrine/norepinephrine: stimulates glycogenolysis and lipolysis.Growth hormone: stimulates glycogenolysis and lipolysis.Note that these factors would complement the effects of glucagon, increasing blood glucose levels.
Hormonal Regulation of Nutrients Right after a meal (resting):- blood glucose elevated- glucagon, cortisol, GH, epinephrine low- insulin increases (due to increased glucose)- Cells uptake glucose, amino acids.- Glucose converted to glycogen, amino acids into protein, lipids stored as triacylglycerol.- Blood glucose maintained at moderate levels.
A few hours after a meal (active):- blood glucose levels decrease- insulin secretion decreases- increased secretion of glucagon, cortisol, GH, epinephrine - glucose is released from glycogen stores (glycogenolysis)- increased lipolysis (beta oxidation)- glucose production from amino acids increases (oxidative deamination; gluconeogenesis)- decreased uptake of glucose by tissues- blood glucose levels maintained Hormonal Regulation of Nutrients
Turnover Rate Rate at which a molecule is broken down and resynthesized.Average daily turnover for carbohydrates is 250 g/day.Some glucose is reused to form glycogen.Only need about 150 g/day.Average daily turnover for protein is 150 g/day.Some protein may be reused for protein synthesis.Only need 35 g/day.9 essential amino acids.Average daily turnover for fats is 100 g/day.Little is actually required in the diet.Fat can be produced from excess carbohydrates.Essential fatty acids:Linoleic and linolenic acids.
Regulation of Energy Metabolism Energy reserves:Molecules that can be oxidized for energy are derived from storage molecules (glycogen, protein, and fat).Circulating substrates:Molecules absorbed through small intestine and carried to the cell for use in cell respiration. Insert fig. 19.2
Pancreatic Islets (Islets of Langerhans) Alpha cells secrete glucagon.Stimulus is decrease in blood [glucose].Stimulates glycogenolysis and lipolysis.Stimulates conversion of fatty acids to ketones.Beta cells secrete insulin.Stimulus is increase in blood [glucose].Promotes entry of glucose into cells.Converts glucose to glycogen and fat.Aids entry of amino acids into cells.
Energy Regulation of Pancreas Islets of Langerhans contain 3 distinct cell types:a cells:Secrete glucagon.b cells:Secrete insulin.D cells: Secrete somatostatin.
Regulation of Insulin and Glucagon Mainly regulated by blood [glucose].Lesser effect: blood [amino acid].Regulated by negative feedback.Glucose enters the brain by facilitated diffusion.Normal fasting [glucose] is 65â105 mg/dl.
Regulation of Insulin and Glucagon (continued) When blood [glucose] increases:Glucose binds to GLUT2 receptor protein in b cells, stimulating the production and release of insulin.Insulin: Stimulates skeletal muscle cells and adipocytes to incorporate GLUT4 (glucose facilitated diffusion carrier) into plasma membranes.Promotes anabolism.
Oral Glucose Tolerance Test Measurement of the ability of b cells to secrete insulin.Ability of insulin to lower blood glucose.Normal personâs rise in blood [glucose] after drinking solution is reversed to normal in 2 hrs. Insert fig. 19.8
Regulation of Insulin and Glucagon Parasympathetic nervous system:Stimulates insulin secretion.Sympathetic nervous system:Stimulates glucagon secretion.GIP:Stimulates insulin secretion.GLP-1:Stimulates insulin secretion.CCK:Stimulates insulin secretion.
Regulation of Insulin and Glucagon Secretion (continued)
Glucose homeostasis â Putting it all together Figure 26.8 Insulin Beta cellsof pancreas stimulatedto release insulin intothe blood Bodycellstake up moreglucose Blood glucose leveldeclines to a set point;stimulus for insulinrelease diminishes Liver takesup glucoseand stores it asglycogen High bloodglucose level STIMULUS:Rising blood glucoselevel (e.g., after eatinga carbohydrate-richmeal) Homeostasis: Normal blood glucose level(about 90 mg/100 mL) STIMULUS:Declining bloodglucose level(e.g., afterskipping a meal) Alphacells ofpancreas stimulatedto release glucagoninto the blood Glucagon Liverbreaks downglycogen and releases glucoseto the blood Blood glucose levelrises to set point;stimulus for glucagonrelease diminishes
Hormonal Regulation of Metabolism Absorptive state:Absorption of energy.4 hour period after eating.Increase in insulin secretion.Postabsorptive state:Fasting state.At least 4 hours after the meal.Increase in glucagon secretion.
Absorptive State Insulin is the major hormone that promotes anabolism in the body.When blood [insulin] increases:Promotes cellular uptake of glucose.Stimulates glycogen storage in the liver and muscles.Stimulates triglyceride storage in adipose cells.Promotes cellular uptake of amino acids and synthesis of proteins.
Postabsorptive State Maintains blood glucose concentration.When blood [glucagon] increased:Stimulates glycogenolysis in the liver (glucose-6-phosphatase).Stimulates gluconeogenesis.Skeletal muscle, heart, liver, and kidneys use fatty acids as major source of fuel (hormone-sensitive lipase).Stimulates lipolysis and ketogenesis.
Insert fig. 19.10 Effect of Feeding and Fasting on Metabolism
Diabetes Mellitus Chronic high blood [glucose].2 forms of diabetes mellitus:Type I: insulin dependent diabetes (IDDM).Type II: non-insulin dependent diabetes (NIDDM).
Comparison of Type I and Type II Diabetes Mellitus Insert table 19.6
Type I Diabetes Mellitus b cells of the islets of Langerhans are destroyed by autoimmune attack which may be provoked by environmental agent.Killer T cells target glutamate decarboxylase in the b cells.Glucose cannot enter the adipose cells.Rate of fat synthesis lags behind the rate of lipolysis.Fatty acids converted to ketone bodies, producing ketoacidosis.Increased blood [glucagon].Stimulates glycogenolysis in liver.
Consequences of Uncorrected Deficiency in Type I Diabetes Mellitus Insert fig. 19.11
Type II Diabetes Mellitus Slow to develop.Genetic factors are significant.Occurs most often in people who are overweight.Decreased sensitivity to insulin or an insulin resistance.Obesity.Do not usually develop ketoacidosis.May have high blood [insulin] or normal [insulin]. Insert fig. 19.12
Treatment in Diabetes Change in lifestyle:Increase exercise:Increases the amount of membrane GLUT-4 carriers in the skeletal muscle cells.Weight reduction.Increased fiber in diet.Reduce saturated fat.
Hypoglycemia Over secretion of insulin.Reactive hypoglycemia:Caused by an exaggerated response to a rise in blood glucose.Occurs in people who are genetically predisposed to type II diabetes. Insert fig. 19.13
Metabolic Regulation Anabolic effects of insulin are antagonized by the hormones of the adrenals, thyroid, and anterior pituitary.Insulin, T3, and GH can act synergistically to stimulate protein synthesis.
The islets of Langerhans are the endocrine cells within the pancreas that secrete four polypeptides with regulatory activity. Two of these, insulin and glucagon, are hormones and have important functions in the regulation of the intermediary metabolism of carbohydrates, proteins, and fats.What is the regulation of the endocrine pancreas? ›
Islets are comprised primarily of alpha cells which produce glucagon, beta cells which secrete insulin, delta cells which release somatostatin and PP cells which produce pancreatic polypeptide. The endocrine pancreas has a dense network of capillaries, so that hormones can be quickly released into the blood stream.What is the role of the pancreatic hormone in carbohydrate metabolism? ›
Insulin is the key hormone of carbohydrate metabolism, it also influences the metabolism of fat and proteins. It lowers blood glucose by increasing glucose transport in muscle and adipose tissue and stimulates the synthesis of glycogen, fat, and protein.What are the three endocrine glands involved in carbohydrate metabolism mark the correct set? ›
Pancreas, adenohypophysis and adrenal gland are three endocrine glands involved in carbohydrate metabolism.