section viii. section viii. tissue metabolism many tissues carry out specialized functions: ch. 43...
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Section VIII.
Section VIII. Tissue metabolism
Many tissues carry out specialized functions:
Ch. 43 – look at different hormones affect metabolism of fuels, especially counter-insulin
Ch. 44 – Proteins and cells of the blood
Ch. 45 – Hemostasis and the clotting cascade
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Chapt. 43
Ch. 43 hormone regulationStudent Learning Outcomes:• Describe the role of hormones in regulating fuel
metabolism – appetite, absorption, transport, oxidation• Explain the main functions of insulin• Explain the role of glucagon• Describe the role of epinephrine, cortisol,
somatostatin, growth hormone and thyroid hormone
• Describe how these hormones exert control quickly by changes in phosphorylation state of enzyme, and more slowly by changes of gene expression
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Table 1 Major hormones affecting fuel metabolism
Glucose uptake Glucose output GlycogenolyisAnabolic Insulin ↑↑ ↓↓ ↓↓
CounterregulatoryGlucagon - ↑↑ ↑↑
Epinephrine - ↑↑ ↑↑ initial
Glucocorticoid ↓ ↑ -
Growth hormone↓ ↑ -
Thyroid hormone - ↑ -
Somatostatin - - -
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I. Insulin
I. Insulin:
Effects on fuel metabolism
(Chapt. 26)
• Stimulates storage of glycogen in liver, muscle• Stimulates synthesis of fatty acids and triagcylglyerols and
storage in adipose tissue• Stimulates synthesis in various tissues of >50 proteins• There are insulinlike growth factors I and II (IGF-1, IGF-II)• Paracrine action: release of insulin from -cells suppresses
secretion of glucagon from -cells.
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II. GlucagonGlucagon• Major insulin counterregulatory hormone• Produced as preglucagon in cells of pancreas• 4 peptides in tandem:
Glicentin-related peptideGlucagonglucagon-related peptide 1 (GLP-1)glucagon-related peptide 2 (GLP-2)
• Proteolytic cleavage releases various combinations
• Different forms in different tissues• Signals through G-protein-coupled receptor to cAMP and PKA
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III. Somatostatin
Fig. 3
Somatostatin: (growth hormone release-inhibiting hormone)
• Preprosomatostatin is 116 aa• Final cyclic 14-aa peptide (SS-14); • From hypothalmus, also secreted cells of pancreas
• In gut, prosomatostatin SS-28 (28-aa) form
• Inhibits release of many hormones:• Growth hormone, TSH, insulin, glucagon,
• 5 receptors, G-protein receptor family – hormone activates inhibitory G; not stimulate cAMP
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Growth hormone
Fig. 1
Growth hormone (somatotropin)stimulates growth:• Made in somatotrophs of anterior pituitary• Direct effects on targets, esp. liver, muscle
• GH receptors are cytosine tyrosine kinases (Janus)
• Indirect, induces insulinlike growth factors (IGF)
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Control of secretion of growth hormone
Control of secretion of GH:• GHRH stimulates release
• GH-releasing hormone• Binds receptors on somatotrophs• Signals by cAMP, Ca2+-calmodulin
• GHRIH (somatostatin) inhibits release• GH-release inhibiting hormone
• IGF-1 feedback from liver• Insulinlike growth factor
• Plasma levels of fuels also control
• See also Table 2 list
Fig. 2
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GHRH and GHRIH
GHRH stimulates release of growth hormone:• Somatocrinin• 40-, 44-aa peptides• Multiple signaling paths
• cAMP, Ca2+-calmodulin
GHRIH inhibits release:• Somatostatin• Binds G-coupled receptors
• Inhibitory G
Fig. 3
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Anabolic effects of growth hormone
Fig. 4
Multiple anabolic effects of growth hormone:• Broad effects on energy metabolism• Uptake, oxidation of fuels
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Production, activity of IGFs
Fig. 5
GH stimulates release of IGFs (liver)• GH receptor is cytoplasmic tyrosine
kinase type (Janus)• IGFs are somatomedins• Structure similar to insulin
• (insulinlike growth factors)• IGF-1 70 aa; IGF-II 67 aa
• IGFs bind membrane RTKs• Increase cell proliferation
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III C. Epinephrine, norepinephrine
Fig. 26.13
Catecholamines epinephrine, norepinephrine• Neurotransmitters or hormones• Stress hormones increase fuel mobilization• Tyrosine precursor
• Adrenergic receptors• 9 different receptors: 6, 3 receptors work through G-protein coupled, adenylyl cyclase, cAMP, PKA receptors G-protein coupled, PIP2-Ca2+
signal transcduction (Fig. 28.10)• Different receptors on different tissues• Mobilize fuels
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Epinephrine
Fig. 6: Epinephrine stimulates fuel metabolism, pancreatic endocrine function.Also stimulates glucagon release to reinforce effects; inhibit insulin
Catecholamines (focus on epinephrine):• Bioamines, stress hormones
Also norepinephrine, dopamine
• Synthesis in adrenal medulla• Act via -adrenergic and -adrenergic receptors
(Ch. 26,28)
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Glucocorticoids (GC)
Fig. 7
Cortisol is major Glucocorticooid:
‘counterregulatory’, ↑blood glucose
Neural and endocrine signals:• Acetylcholine & serotonin:• CRH = corticotropin-releasing hormone
(midbrain)• ACTH = adrenocorticotropic hormone • Adrenal gland releases cortisol• Cortisol does negative feedback (but
overridden by stress)
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Effects of Glucocorticoids (GC)
Fig. 8 fuel metabolic effects
Glucocorticoids (GC) have diverse effects:• bind intracellular receptors, bind DNA, induce
transcription of target genes• Fuel metabolism effects
often stimulate degradation• Also nonmetabolic effects
(Table 3)
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Signal transduction by cortisol, intracellular receptors
Cortisol and thyroid hormone bind intracellular receptors:
• Binding of hormone causes hormone-receptor complex to bind specific DNA sequences, increase transcription from target genes.
Figs. 11.7,8
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Thyroid hormone (TH)
E. Thyroid hormone (TH) is derived from tyrosine:
• T3 and T4 made in thyroid acinar cells• signal by binding intracellular nuclear receptors
Fig. 9
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Formation of thyroid hormone
Fig. 10
Formation of thyroid hormone (TH):• Protein thyroglobulin secreted into colloid space• Iodination, coupling• Pinocytosis • Digestion by lysosomes
• ~ 10:1 T4:T3
• Synthesis stimulated byTSH in anterior pituitary
• TSH stimulates release T1/2 days in plasma
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Regulation of TH levels
Fig. 11
Regulation of TH levels:• TRH = thyrotropin-releasing hormone• TSH = thyroid-stimulating hormone
• TSH binds membrane receptor, ↑cAMP• Also through IP3 + DAG, Ca2+
• T3 & T4 secreted from thyroid
• T3 inhibits release of TSH, TRH
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Physiological effects thyroid hormone
Normal TH affects fuel metabolism:Liver: carbohydrate, lipid metabolism
• Increase glycolysis, cholesterol synthesis• Increase sensitivity of hepatocyte to gluconeogenic &
glycogenolyticactions of epinephrine
Adipocytes: • sensitizes adipocyte to lipolytic action of epinephrine • also increase availability of glucose to fat cells
Muscle: increase glucose uptake, stimulate protein synthesis
TH can increase heat production by stimulating ATP utilization in futile cycles (increase heat production by uncoupling)
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F. GI hormones affect fuel metabolism
Fig. 12
Many GI hormones affect fuel metabolism:• Direct and indirect effects: produced by many tissues (Table 4,5)• GLP-1, glucagonlike peptide; GIP, Gastic inhibitory peptide • CCK, cholecystokinin has indirect effects
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Key concepts
Key concepts:• Insulin is major anabolic hormone• Counterregulatory (counterinsulin) hormones include:
• Glucagon• Somatostatin• Growth hormone has diverse roles
• Catecholamine hormones• Cortisol (glucacorticoid) promtoes survival• Thyroid hormones secretion is highly regulated• Intestines and stomach secrete hormones (incretins)
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Review question
Review question.3. A dietary deficiency of iodine will lead to which of the
following?a.A direct effect on the synthesis of thyroglobulin on
ribosomesb.An increased secretion of thyroid-stimulatory hormone
(TSH)c.Decreased production of thyrotropin-releasing hormone
(TRH)d.Increased heat productione.Weight loss