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Round One: Insulin and Glucagon
Round Two: PTH and Calcitonin
Antagonistic hormones are actually pairs of hormones that work against each other. As we will see, though insulin and glucogon or PTH and Calcitonin work on the same systems, they are constantly fighting against each other in order to maintain homeostasis.
How does this hormone utilize signal transduction pathways to cause an effect?
Start video at 2:08
- Receptor activation leads to the phosphorylation of key tyrosine residues on IRS proteins, which activates the PI3-kinase (a lipid kinase). The catalytic subunit of PI3-kinase, then phosphorylates phosphatidylinositol (4,5) bisphosphate [PtdIns(4,5)P2] which leads to the formation of Ptd(3,4,5)P3. As a result, AKT is recruited to the plasma membrane. Then AKT is phosphorylated by protein kinases. Once active, AKT enters the cytoplasm where it leads to the phosphorylation and inactivation of glycogen synthase kinase 3 (GSK3). A major substrate of GSK3 is glycogen synthase, an enzyme that catalyzes the final step in glycogen synthesis. Phosphorylation of glycogen synthase by GSK3 inhibits glycogen synthesis; therefore the inactivation of GSK3 by AKT promotes glucose storage as glycogen.
Transduced signal triggers a specific action by the target cell:
- Increases cellular uptake of glucose.
- Increases formation of glycogen from glucose in liver/(skeletal) muscle cells.
- Increases rate of intracellular catabolism of glucose.
- Increases fat synthesis from glucose in liver cells and adipose tissue.
Insulin acts as the signaling molecule that comes from outside the cell. It binds to a insulin receptor protein embedded in the cell membrane.
Parathyroid Hormone (PTH)
Insulin
- Insulin is created in the Pancreas.
- Insulin is made of two peptide chains called the A and B chains which are linked together by disulfide bonds. In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids.
- The liver is the main target organ for Insulin, however most tissue in the body requires insulin, so insulin also targets all cells, except the brain cells. Insulin lowers the blood sugar level by instructing cells to take glucose out of the blood and store it.
- Insulin is controlled and regulated by the islets of Langerhans which are specialized beta cells in the Pancreas that detect an increase in sugar concentration in the blood. Then they release insulin to lower the blood sugar levels.
- The normal function of insulin is to lower sugar levels in blood. It causes glucose to be stored as glycogen. When glucose is stored, it is removed from the blood stream.
If calcium levels in the bones/urine decrease or absorbtion in the instestines increases, PTH is winning.
If there is more calcium in the bones, more calcium in the urine, or less calcium absorbed in the intestinces, calcitonin is winning.
Schlichte, Martin. "Signal Transduction and Hormones." Lecturio Medical Magazine. Lecturio GmbH, 18 Sept. 2015. Web. 28 Oct. 2015. <https://www.lecturio.com/magazine/signal-transduction-and-hormones/>
Bowen, R. "Calcium and Phosphorus Homeostasis." Calcium and Phosphorus Homeostasis. Colorado State University, 11 Oct. 2003. Web. 28 Oct. 2015. <http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/calcium.html>
Bowen, R. "Calcitonin." Calcitonin. Colorado State University, 11 Oct. 2003. Web. 29 Oct. 2015. <http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/calcitonin.html>
Hasudungan, Armando. "Endocrinology - Calcium and Phosphate Regulation." YouTube. YouTube, 19 May 2015. Web. 29 Oct. 2015. <
Kamerzell, Tim J., Sangeeta B. Joshi, Donald McClean, Lori Peplinskie, Karen Toney, Damon Papac, Meili Li, and C. Russell Middaugh. "Parathyroid Hormone Is a Heparin/polyanion Binding Protein: Binding Energetics and Structure Modification." Protein Science : A Publication of the Protein Society. Cold Spring Harbor Laboratory Press, June 2007. Web. 29 Oct. 2015. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2206658/>
"You & Your Hormones." You & Your Hormones. Society for Endocrinology, 21 Jan. 2015. Web. 29 Oct. 2015. <http://www.yourhormones.info/Hormones/Parathyroid_hormone.aspx>
"You & Your Hormones." You & Your Hormones. Society for Endocrinology, 19 Feb. 2015. Web. 29 Oct. 2015. <http://www.yourhormones.info/hormones/glucagon.aspx>
Hooper, Claude, PhD. "Overview of Insulin Signaling Pathways." An Overview of Insulin Signaling Pathways. Abcam Plc, n.d. Web. 01 Nov. 2015. <http://www.abcam.com/pathways/overview-of-insulin-signaling-pathways>
"You & Your Hormones." You & Your Hormones. Society for Endocrinology, 19 Feb. 2015. Web. 01 Nov. 2015. <http://www.yourhormones.info/hormones/insulin.aspx>
Calcitonin
Insulin and Glucagon fight to maintain homeostasis at 90 mg of glucose for every 100mL of blood.
If there are high levels of glucose in the blood but they are decreased in order to maintain homeostasis, the insulin is working harder and winning.
If there are low levels of glucose in the blood but they are increased in order to maintain homeostasis, the glucagon is working harder and winning.
- Calcitonin is produced by the parafollicular cells, otherwise known as C-cells of the Thyriod gland.
- It is made of a single chain of 32 amino acids containing a single disulfide bond and a ring shaped amino terminus.
- The target organs of Calcitonin are the bones, kidneys, and intestines.
- Calcitonin uses feedback inhibition to regulate Calcium levels in the blood.
- The main function of Calcitonin is to reduce Calcium levels when they are higher than they should be. When high Calcium levels are detected, the secretion of Calcitonin is stimultated.
- Similarly, when Calcium levels are lower than they should be, the production of Calcitonin is stopped.
- In the bones, Calcitonin supresses the reabsorption of Calcium by inhibiting osteoclast activity.
-Osteoclasts are a type of cell that "digests" bone. The inhibition of osteoclasts leads to the release of calcium and phosphorus into the blood. At the same time, Calcitonin stimulates osteoblasts which increase the production of new bone tissue.
- In the kidneys, where Calcium is usually reabsorbed, it is excreted through the urine in higher concentrations.
- The effects of Calcitonin oppose those of the Parathyroid Hormone.
Glucagon
PTH and calcitonin do opposite tasks, but they work together to maintain homeostasis and calcium levels in the body.
Insulin and Glucagon do opposite tasks, but they work together to maintain homeostasis and glucose levels in the body.