Insulin: Difference between revisions

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[[Image:Insulin.gif|right|Insulin chain A and B. For interactive figures, scroll down and click on green links]]

[[Image:Insulin.gif|right|frame|Insulin chain A and B. For interactive figures, scroll down and click on green links]]

'''Insulin''' is a peptide hormone that helps to maintain blood sugar within a healthy range by regulating [[Carbohydrate Metabolism|carbohydrate]] and lipid metabolism throughout the body~~<ref>PMID:10927996</ref><ref>DOI:10.1111/dom.13402</ref>~~. It is secreted by specialized cells in the pancreas and acts by binding to [[insulin receptor|insulin receptors]] on other cells. Insulin in its mature form contains two peptide chains connected by disulfide crosslinks, and occurs either as monomer or as hexamer. Administering insulin in carefully determined doses at the appropriate times is used in managing [[diabetes]], a chronic condition where the body fails to maintain blood sugar levels by itself.

'''Insulin''' is a peptide [[hormone]] that helps to maintain blood sugar within a healthy range by regulating [[Carbohydrate Metabolism|carbohydrate]] and lipid metabolism throughout the body. It is secreted by specialized cells in the pancreas and acts by binding to [[insulin receptor|insulin receptors]] on other cells. Insulin in its mature form contains two peptide chains connected by [[Cystine|disulfide crosslinks]], and occurs either as monomer or as hexamer. Administering insulin in carefully determined doses at the appropriate times is used in managing [[diabetes]], a chronic condition where the body fails to maintain blood sugar levels by itself.

*'''Proinsulin''' is the insulin precursor which is converted in the pancreas to insulin and C-peptide<ref>PMID:403392</ref>.

*'''Leginsulin''' is an insulin-like peptide found in legumes <ref>PMID:30442953</ref>.

*'''Insulin lispro''' is recombinant insulin which has more rapid absorption than regular insulin<ref>PMID:9339963</ref>. See also [[Insulin lispro]].

*'''Insulin glargine''' is a long-acting insulin <ref>PMID:10730548</ref>. See also [[Insulin glargine]].

*'''Insulin detemir''' is a long-acting analog used for patients with type 1 or 2 diabetes <ref>PMID:23110609</ref>.

*'''Insulin desB30''' is an insulin with B chain lacking residue 30 (The) <ref>PMID:31039402</ref>.

==Other Proteopedia pages about or relating to insulin==

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[[Diabetes & Hypoglycemia]]

[[Insulin (Hebrew)]]

[[Insulin ~~glargine~~]]

[[Insulin aspart]]

[[Insulin_mo-or-sl|Insulin and pro-insulin (Hebrew)]]

[[Insulin-Degrading Enzyme]]

[[Molecular_Playground/Insulin]]

[[Insulin Structure & Function]]

[[Insulin ~~3D Structures~~]]

[[Insulin signal transduction pathway]]

'''Proteins that interact with insulin'''

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[[Insulin receptor]]

[[Insulin-like growth factor receptor]]

'''Tutorials we would love to see'''

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[[Image:Glucose insulin day.png|300px|left|thumb|Schematic of daily changes of blood sugar (red) and insulin (blue)]]

Our blood sugar level (i.e. glucose concentration) varies over time with food intake and exercise, but has to remain in a narrow range so we stay healthy (not become hyperglycemic or hypoglycemic). Insulin, together with [[glucagon]], regulates blood sugar levels by changing fuel metabolism in all metabolic cells (e.g. liver, fat, kidney, muscle and nerve cells) <ref>https://www.yourhormones.info/hormones/insulin/</ref> ~~on a timescale of minutes and hours~~. In simplest terms, the presence of insulin in the blood signals the well-fed stage, while the presence of glucagon signals the fasting stage.

Our blood sugar level (i.e. glucose concentration) varies over time with food intake and exercise, but has to remain in a narrow range so we stay healthy (not become hyperglycemic or hypoglycemic). Insulin, together with [[glucagon]], regulates blood sugar levels by changing fuel metabolism in all metabolic cells (e.g. liver, fat, kidney, muscle and nerve cells) on a timescale of minutes and hours<ref>https://www.yourhormones.info/hormones/insulin/</ref><ref>PMID:10927996</ref><ref>DOI:10.1111/dom.13402</ref>. In simplest terms, the presence of insulin in the blood signals the well-fed stage, while the presence of glucagon signals the fasting stage.

Biosynthesis and processing of insulin occurs in the [https://en.wikipedia.org/wiki/Beta_cell beta cells] of the pancreas. The beta cells are found in the islets of Langerhans, which also contain the alpha cells that synthesize glucagon. Insulin is made as a 110 amino acid pre-proinsulin, which is processed to the mature 51 amino acid insulin and targeted to secretory vesicles. In a healthy adult, about 200 units of insulin are available in the pancreas, of which 30-50 units are secreted daily<ref>https://www.britannica.com/science/insulin</ref>. With a unit of insulin corresponding to 0.0347 mg mature insulin <ref>https://www.who.int/biologicals/expert_committee/BS_2143_Human_Recombinant_Insulin_final.pdf</ref>, the body contains only about 7 mg of insulin. In its stored form, insulin is a hexamer complexed to zinc ions.

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===Receptor interaction===

The insulin receptor belongs to the class of tyrosine kinase receptors ~~(a ][Category:Receptor_protein-tyrosine_kinase|large protein family)~~. Many of these receptors occur as monomers that dimerize upon ligand binding, bringing the intracellular tytrosine kinase domains (the endodomains) into close vicinity. In contrast, the insulin receptor (just like the closely related [[IGF1#Stimulating_interaction_:_IGF-1_-_IGF-1R|IGF-1 receptor]]) is a dimer even in the absence of ligand, crosslinked by disulfide bridges. The unliganded receptor ectodomain has the shape of a Λ (an inverted V), keeping the transmembrane segments and the endodomains at a distance.

The insulin receptor belongs to the class of [[tyrosine kinase]] receptors. Many of these receptors occur as monomers that dimerize upon ligand binding, bringing the intracellular tytrosine kinase domains (the endodomains) into close vicinity. In contrast, the insulin receptor (just like the closely related [[IGF1#Stimulating_interaction_:_IGF-1_-_IGF-1R|IGF-1 receptor]]) is a dimer even in the absence of ligand, crosslinked by disulfide bridges. The unliganded receptor ectodomain has the shape of a Λ (an inverted V), keeping the transmembrane segments and the endodomains at a distance.

Cryo-electronmicroscopy studies have shown a [http://proteopedia.org/wiki/images/0/05/LambdaTee.gif Λ to T transition] when insulin binds. One structure resolves four <scene name='82/821037/Spacefilling/5'>insulin binding sites</scene> (1, 1', 2, 2') per receptor dimer<ref name="ecto">DOI:10.1101/679233 </ref> (coordinates not yet available). Contacts with insulin are distinct in site 1 vs. site 2, as are the conformations of insulin<ref>PMID:25092300</ref>. For comparison to the initial scene, here is another view of the <scene name='82/821037/Ribbon/2'>contact residues</scene>.

[[Cryo-EM|Cryo-electronmicroscopy]] studies have shown a [http://proteopedia.org/wiki/images/0/05/LambdaTee.gif Λ to T transition] when insulin binds. One structure resolves four <scene name='82/821037/Spacefilling/5'>insulin binding sites</scene> (1, 1', 2, 2') per receptor dimer<ref name="ecto">DOI:10.1101/679233 </ref> (coordinates not yet available). Contacts with insulin are distinct in site 1 vs. site 2, as are the conformations of insulin<ref>PMID:25092300</ref>. For comparison to the initial scene, here is another view of the <scene name='82/821037/Ribbon/2'>contact residues</scene>.

<scene name='82/821037/Receptor_bound/1'>Binding sites 1 and 1'</scene> had already been characterized in previous structures<ref>PMID:29512653</ref><ref name="gutmann"/>. Insulin makes contacts with both the N-terminal domain <jmol>

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</StructureSection>

==Insulin 3D structures==

[[Insulin 3D Structures]]

==See also==

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@@ Line 1: / Line 1: @@
-[[Image:Insulin.gif|right|Insulin chain A and B. For interactive figures, scroll down and click on green links]]
+[[Image:Insulin.gif|right|frame|Insulin chain A and B. For interactive figures, scroll down and click on green links]]
-'''Insulin''' is a peptide hormone that helps to maintain blood sugar within a healthy range by regulating [[Carbohydrate Metabolism|carbohydrate]] and lipid metabolism throughout the body<ref>PMID:10927996</ref><ref>DOI:10.1111/dom.13402</ref>. It is secreted by specialized cells in the pancreas and acts by binding to [[insulin receptor|insulin receptors]] on other cells. Insulin in its mature form contains two peptide chains connected by disulfide crosslinks, and occurs either as monomer or as hexamer. Administering insulin in carefully determined doses at the appropriate times is used in managing [[diabetes]], a chronic condition where the body fails to maintain blood sugar levels by itself.
+'''Insulin''' is a peptide [[hormone]] that helps to maintain blood sugar within a healthy range by regulating [[Carbohydrate Metabolism|carbohydrate]] and lipid metabolism throughout the body. It is secreted by specialized cells in the pancreas and acts by binding to [[insulin receptor|insulin receptors]] on other cells. Insulin in its mature form contains two peptide chains connected by [[Cystine|disulfide crosslinks]], and occurs either as monomer or as hexamer. Administering insulin in carefully determined doses at the appropriate times is used in managing [[diabetes]], a chronic condition where the body fails to maintain blood sugar levels by itself.
+*'''Proinsulin''' is the insulin precursor which is converted in the pancreas to insulin and C-peptide<ref>PMID:403392</ref>.
+*'''Leginsulin''' is an insulin-like peptide found in legumes <ref>PMID:30442953</ref>.
+*'''Insulin lispro''' is recombinant insulin which has more rapid absorption than regular insulin<ref>PMID:9339963</ref>.  See also [[Insulin lispro]].
+*'''Insulin glargine''' is  a long-acting insulin <ref>PMID:10730548</ref>.  See also [[Insulin glargine]].
+*'''Insulin detemir''' is a long-acting analog used for patients with type 1 or 2 diabetes <ref>PMID:23110609</ref>.
+*'''Insulin desB30''' is an insulin with B chain lacking residue 30 (The) <ref>PMID:31039402</ref>.
 ==Other Proteopedia pages about or relating to insulin==
@@ Line 8: / Line 14: @@
 [[Diabetes & Hypoglycemia]]<br>
 [[Insulin (Hebrew)]]<br>
-[[Insulin glargine]]<br>
+[[Insulin aspart]]<br>
 [[Insulin_mo-or-sl|Insulin and pro-insulin (Hebrew)]]<br>
 [[Insulin-Degrading Enzyme]]<br>
 [[Molecular_Playground/Insulin]]<br>
 [[Insulin Structure & Function]]<br>
-[[Insulin 3D Structures]]<br>
+[[Insulin signal transduction pathway]]<br>
 '''Proteins that interact with insulin'''
@@ Line 21: / Line 27: @@
 [[Insulin receptor]]<br>
 [[Insulin-like growth factor receptor]]<br>
 '''Tutorials we would love to see'''
@@ Line 30: / Line 37: @@
 [[Image:Glucose insulin day.png|300px|left|thumb|Schematic of daily changes of blood sugar (red) and insulin (blue)]]
-Our blood sugar level (i.e. glucose concentration) varies over time with food intake and exercise, but has to remain in a narrow range so we stay healthy (not become hyperglycemic or hypoglycemic). Insulin, together with [[glucagon]], regulates blood sugar levels by changing fuel metabolism in all metabolic cells (e.g. liver, fat, kidney, muscle and nerve cells) <ref>https://www.yourhormones.info/hormones/insulin/</ref> on a timescale of minutes and hours. In simplest terms, the presence of insulin in the blood signals the well-fed stage, while the presence of glucagon signals the fasting stage.
+Our blood sugar level (i.e. glucose concentration) varies over time with food intake and exercise, but has to remain in a narrow range so we stay healthy (not become hyperglycemic or hypoglycemic). Insulin, together with [[glucagon]], regulates blood sugar levels by changing fuel metabolism in all metabolic cells (e.g. liver, fat, kidney, muscle and nerve cells) on a timescale of minutes and hours<ref>https://www.yourhormones.info/hormones/insulin/</ref><ref>PMID:10927996</ref><ref>DOI:10.1111/dom.13402</ref>. In simplest terms, the presence of insulin in the blood signals the well-fed stage, while the presence of glucagon signals the fasting stage.
 Biosynthesis and processing of insulin occurs in the [https://en.wikipedia.org/wiki/Beta_cell beta cells] of the pancreas. The beta cells are found in the islets of Langerhans, which also contain the alpha cells that synthesize glucagon. Insulin is made as a 110 amino acid pre-proinsulin, which is processed to the mature 51 amino acid insulin and targeted to secretory vesicles. In a healthy adult, about 200 units of insulin are available in the pancreas, of which 30-50 units are secreted daily<ref>https://www.britannica.com/science/insulin</ref>. With a unit of insulin corresponding to 0.0347 mg mature insulin <ref>https://www.who.int/biologicals/expert_committee/BS_2143_Human_Recombinant_Insulin_final.pdf</ref>, the body contains only about 7 mg of insulin. In its stored form, insulin is a hexamer complexed to zinc ions.
@@ Line 117: / Line 124: @@
 ===Receptor interaction===
-The insulin receptor belongs to the class of tyrosine kinase receptors (a ][Category:Receptor_protein-tyrosine_kinase|large protein family). Many of these receptors occur as monomers that dimerize upon ligand binding, bringing the intracellular tytrosine kinase domains (the endodomains) into close vicinity. In contrast, the insulin receptor (just like the closely related [[IGF1#Stimulating_interaction_:_IGF-1_-_IGF-1R|IGF-1 receptor]]) is a dimer even in the absence of ligand, crosslinked by disulfide bridges. The unliganded receptor ectodomain has the shape of a Λ (an inverted V), keeping the transmembrane segments and the endodomains at a distance.
+The insulin receptor belongs to the class of [[tyrosine kinase]] receptors. Many of these receptors occur as monomers that dimerize upon ligand binding, bringing the intracellular tytrosine kinase domains (the endodomains) into close vicinity. In contrast, the insulin receptor (just like the closely related [[IGF1#Stimulating_interaction_:_IGF-1_-_IGF-1R|IGF-1 receptor]]) is a dimer even in the absence of ligand, crosslinked by disulfide bridges. The unliganded receptor ectodomain has the shape of a Λ (an inverted V), keeping the transmembrane segments and the endodomains at a distance.
-Cryo-electronmicroscopy studies have shown a [http://proteopedia.org/wiki/images/0/05/LambdaTee.gif Λ to T transition] when insulin binds. One structure resolves four <scene name='82/821037/Spacefilling/5'>insulin binding sites</scene> (1, 1', 2, 2') per receptor dimer<ref name="ecto">DOI:10.1101/679233 </ref> (coordinates not yet available). Contacts with insulin are distinct in site 1 vs. site 2, as are the conformations of insulin<ref>PMID:25092300</ref>. For comparison to the initial scene, here is another view of the <scene name='82/821037/Ribbon/2'>contact residues</scene>.
+[[Cryo-EM|Cryo-electronmicroscopy]] studies have shown a [http://proteopedia.org/wiki/images/0/05/LambdaTee.gif Λ to T transition] when insulin binds. One structure resolves four <scene name='82/821037/Spacefilling/5'>insulin binding sites</scene> (1, 1', 2, 2') per receptor dimer<ref name="ecto">DOI:10.1101/679233 </ref> (coordinates not yet available). Contacts with insulin are distinct in site 1 vs. site 2, as are the conformations of insulin<ref>PMID:25092300</ref>. For comparison to the initial scene, here is another view of the <scene name='82/821037/Ribbon/2'>contact residues</scene>.
 <scene name='82/821037/Receptor_bound/1'>Binding sites 1 and 1'</scene> had already been characterized in previous structures<ref>PMID:29512653</ref><ref name="gutmann"/>. Insulin makes contacts with both the N-terminal domain <jmol>
@@ Line 134: / Line 141: @@
 </StructureSection>
+==Insulin 3D structures==
+[[Insulin 3D Structures]]
 ==See also==