CSB325 Lecture 8 Review Notes

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Cell and Systems Biology
David Lovejoy

CSB325 Lecture 9 – Energy and Stress Glucose metabolism GHRH and PACAP (paralogues)  somatotrophs in the anterior pituitary GH - Hexokinase (glucose  glucose-6-phosphate) - Stomach  ghrelin (direct)  positive feedback on somatotrophs (GH) - Glycogen synthetase (glucose-6-phosphate  glycogen) - Glucose-6-phosphatase (glucose-6-phosphate  glucose - Adipocytes  leptin (indirect)  positive feedback on GH-releasing factors (NPY, bombesin, CCK)  positive feedback on somatotrophs (GH) Pancreas - Endocrine component - Somatotrophs  activin (short-loop positive feedback)  positive o Islets of Langerhans secrete insulin and glucagon feedback on somatotrophs (GH) - Somatotrophs  GH (positive autoregulation)  positive feedback on - Exocrine component o Ductile cells secrete bicarbonate somatotrophs (GH) o Acinar cells secrete digestive enzymes - Liver  IGF-I & IGF-II (long-loop negative feedback)  negative feedback on somatotrophs (GH) Distribution of insulin-, glucagon-, and somatostatin-containing cells - Rat islet GH-releasing factors o Glucagon-containing cells (clustered) and somatostatin- - GHRH containing cells (clustered) are at the periphery of the islet, and - PACAP insulin-containing cells (dispersed) are centrally located - GnRH, dopamine, TRH - Human islet - NPY, bombesin, CCK o The islet is divided into smaller subunits GH-inhibiting factors o Each subunit contains glucagon-containing cells (clustered) and - Somatostatin (SRIF) somatostatin-containing cells (clustered) at the periphery of the - Serotonin, norepinephrine, glutamate islet, and insulin-containing cells (dispersed) are centrally located Actions of GH on carbohydrate, lipid, and protein metabolism Endocrine cells in the islets of Langerhans of the pancreas - Liver - Alpha cells (A cells)  Glucagon, GLP-1 and GLP-2 o ↑ VLDL secretion - Beta cells (B cells)  Insulin, C-peptide, Amylin, GABA, PTHrP o ↑ HL activity - Delta cells (D cells)  Somatostatin o ↓ PPARα expression - PP cells (F cells)  Polypeptide o ↑ production and uptake of IDL, LDL, HDL Insulin o ↑ protein synthesis - Stimulated by glucose - Bone o ↑ mineral accretion - ↑ glucose uptake - ↑ glycogen formation o ↑ bone mass - ↑ lipogenesis - Muscle o ↓ glucose uptake - ↑ lipid accumulation - ↑ amino acid uptake o ↑ LPL activity - ↓ glycogen mobilization o ↑ β-oxidation o ↑ protein synthesis - ↓ amino acid mobilization - ↓ gluconeogenesis - Adipose - ↓ lipolysis o ↑ lipolysis  ↓ lipogenesis Glucagon - Stimulated by fasting, stress, protein-rich diet  ↓ re-esterification of FFA - Major functional antagonist of insulin  ↓ glucose uptake  ↓ body fat mass Adrenal gland - Adrenal medulla (called head kidney in fishes) o Made up of nervous tissue o Produces catecholamines (epinephrine, norepinephrine) - Adrenal cortex (called interrenal gland in fishes) o Made up of epithelial tissue o Produces steroids (cortisol, corticosterone, aldosterone, testosterone, estradiol, glucocorticoids) - Epinephrine o Activated by emotional stress  Emotional stress tends to utilize glucose resources and protect adipose supplies o ↑ glycogenolysis (glycogen breakdown) o ↑ glycolysis (glucose breakdown) o ↑ blood glucose - Norepinephrine o Activated by physical stress (e.g., hypotension, hypoglycemia, blood loss, hypoxia, cold, fright)  Physical stress tends to utilize adipose resources and protect glucose supplies o ↑ lipolysis (FFA breakdown) o ↑ blood FFA Hypothalamus-pituitary-thyroid (HPT) axis Hypothalamus-pituitary-adrenal (HPA) axis - CRF is secreted into the vasculature at the median eminence by the paraventricular nucleus in the hypothalamus - TRH is secreted into the vasculature at the median eminence by the paraventricular nucleus in the hypothalamus Interaction between CRF and TRH Interaction between CRF and NPY - CRF and TRH can have positive and reciprocal actions on the release of each other in the PVN Stress responses Supraoptic nucleus (SON) - Three basic phases - Magnocellular cells o Phase 1 = catecholamines o AVP containing cells, which project to the posterior pituitary  Epinephrine (e.g., osmoregulatory response)  Norepinephrine  stimulates HPA axis Note: Vasopressin and oxytocin released from the PVN are associated with the o Phase 2 = cortisol activity stress response, but vasopressin and oxytocin released from the SON are associated  ACTH with osmoregulatory respons
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