Blood sugar regulation

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Ball-and-stick model of a glucose molecule D-glucose-chain-3D-balls.png
Ball-and-stick model of a glucose molecule

Blood sugar regulation is the process by which the levels of blood sugar, the common name for glucose dissolved in blood plasma, are maintained by the body within a narrow range.

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The regulation of glucose levels through Homeostasis Glucose Homeostasis for Wikipedia.jpg
The regulation of glucose levels through Homeostasis

This tight regulation is referred to as glucose homeostasis. Insulin, which lowers blood sugar, and glucagon, which raises it, are the most well known of the hormones involved, but more recent discoveries of other glucoregulatory hormones have expanded the understanding of this process. The gland called pancreas secretes two hormones and they are primarily responsible to regulate glucose levels in blood. [1]

Mechanisms

The flat line is the optimal blood sugar level (i.e. the homeostatic set point). Blood sugar levels are balanced by the tug-of-war between 2 functionally opposite hormones, glucagon and insulin. Negative Feedback Gif.gif
The flat line is the optimal blood sugar level (i.e. the homeostatic set point). Blood sugar levels are balanced by the tug-of-war between 2 functionally opposite hormones, glucagon and insulin.

Blood sugar levels are regulated by negative feedback in order to keep the body in balance. [2] [3] [4] [5] The levels of glucose in the blood are monitored by many tissues, but the cells in the pancreatic islets are among the most well understood and important.[ citation needed ]

Granule docking is an important glucose-dependent step in human insulin secretion that does not work properly in type 2 diabetes. [6]

Glucagon

If the blood glucose level falls to dangerously low levels (as during very heavy exercise or lack of food for extended periods), the alpha cells of the pancreas release glucagon, a peptide hormone which travels through the blood to the liver, where it binds to glucagon receptors on the surface of liver cells and stimulates them to break down glycogen stored inside the cells into glucose (this process is called glycogenolysis). The cells release the glucose into the bloodstream, increasing blood sugar levels. Hypoglycemia, the state of having low blood sugar, is treated by restoring the blood glucose level to normal by the ingestion or administration of dextrose or carbohydrate foods. It is often self-diagnosed and self-medicated orally by the ingestion of balanced meals. In more severe circumstances, it is treated by injection or infusion of glucagon.[ citation needed ]

Insulin

When levels of blood sugar rise, whether as a result of glycogen conversion, or from digestion of a meal, a different hormone is released from beta cells found in the islets of Langerhans in the pancreas. This hormone, insulin, causes the liver to convert more glucose into glycogen (this process is called glycogenesis), and to force about 2/3 of body cells (primarily muscle and fat tissue cells) to take up glucose from the blood through the GLUT4 transporter, thus decreasing blood sugar. When insulin binds to the receptors on the cell surface, vesicles containing the GLUT4 transporters come to the plasma membrane and fuse together by the process of endocytosis, thus enabling a facilitated diffusion of glucose into the cell. As soon as the glucose enters the cell, it is phosphorylated into glucose-6-phosphate in order to preserve the concentration gradient so glucose will continue to enter the cell. [7] Insulin also provides signals to several other body systems, and is the chief regulator of metabolic control in humans.[ citation needed ]

There are also several other causes for an increase in blood sugar levels. Among them are the 'stress' hormones such as epinephrine (also known as adrenaline), several of the steroids, infections, trauma, and of course, the ingestion of food.[ citation needed ]

Diabetes mellitus type 1 is caused by insufficient or non-existent production of insulin, while type 2 is primarily due to a decreased response to insulin in the tissues of the body (insulin resistance). Both types of diabetes, if untreated, result in too much glucose remaining in the blood (hyperglycemia) and many of the same complications. Also, too much insulin and/or exercise without enough corresponding food intake in diabetics can result in low blood sugar (hypoglycemia).[ citation needed ]

Hormones that influence blood glucose level

HormoneTissue of originMetabolic effectEffect on blood glucose
Insulin Pancreatic β Cells 1) Enhances entry of glucose into cells; 2) Enhances storage of glucose as glycogen, or conversion to fatty acids; 3) Enhances synthesis of fatty acids and proteins; 4) Suppresses breakdown of proteins into amino acids, and Triglycerides (from adipose tissue) into free fatty acids.Lowers
Amylin [1] Pancreatic β Cells 1) Suppresses glucagon secretion after eating; 2) Slows gastric emptying; 3) Reduces food intake.Lowers
GLP-1 [1] Intestinal L cells 1) Enhances glucose-dependent insulin secretion; 2) Suppresses glucagon secretion after eating; 3) Slows gastric emptying; 4) Reduces food intake. (Only works while food is in the gut)Lowers
GIP Intestinal K cells1) Induce insulin secretion 2) Inhibits apoptosis of the pancreatic beta cells and promotes their proliferation 3) Stimulates glucagon secretion and fat accumulationLowers
Glucagon Pancreatic α Cells 1) Enhances release of glucose from glycogen (glycogenolysis); 2) Enhances synthesis of glucose (gluconeogenesis) from amino acids or fats.Raises
Asprosin [8] White adipose tissue 1) Enhances release of liver glucose during fasting.Raises
Somatostatin Pancreatic δ Cells 1) Suppresses glucagon release from α cells (acts locally); 2) Suppresses release of Insulin, Pituitary tropic hormones, gastrin and secretin. 3) Decreases stomach acid production by preventing the release of other hormones (gastrin and histamine), thus slowing down the digestive process.Lowers[ citation needed ]
Epinephrine Adrenal medulla 1) Enhances release of glucose from glycogen; 2) Enhances release of fatty acids from adipose tissue.Raises
Cortisol Adrenal cortex 1) Enhances gluconeogenesis; 2) Antagonizes insulin.Raises
ACTH Anterior pituitary 1) Enhances release of cortisol; 2) Enhances release of fatty acids from adipose tissue.Raises
Growth hormone Anterior pituitary Antagonizes insulinRaises
Thyroxine Thyroid 1) Enhances release of glucose from glycogen; 2) Enhances absorption of sugars from intestine.Raises

Carbohydrate Control in Invertebrates

Insects have two types of „blood sugar", the monosaccharide glucose and the disaccharide trehalose. Trehalose is the major carbohydrate used by insects for flight. [9]

The concentrations of the carbohydrates trehalose and glucose in the insect hemolymph are tightly controlled by multiple enzymes and hormones, including trehalase, insulin-like peptides (ILPs and DILPs), adipokinetic hormone (AKH), leucokinin (LK), octopamine and other mediators, thereby maintaining carbohydrate homeostasis by endocrine and metabolic feedback mechanisms. [10] [11] [12] [13]

Related Research Articles

<span class="mw-page-title-main">Glucose</span> Naturally produced monosaccharide

Glucose is a sugar with the molecular formula C6H12O6. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using energy from sunlight. It is used by plants to make cellulose, the most abundant carbohydrate in the world, for use in cell walls, and by all living organisms to make adenosine triphosphate (ATP), which is used by the cell as energy.

<span class="mw-page-title-main">Hypoglycemia</span> Decrease in blood sugar

Hypoglycemia, also spelled hypoglycaemia or hypoglycæmia, sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly.

<span class="mw-page-title-main">Insulin</span> Peptide hormone

Insulin is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (INS) gene. It is the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats, and protein by promoting the absorption of glucose from the blood into cells of the liver, fat, and skeletal muscles. In these tissues the absorbed glucose is converted into either glycogen, via glycogenesis, or fats (triglycerides), via lipogenesis; in the liver, glucose is converted into both. Glucose production and secretion by the liver are strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is thus an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules in the cells. Low insulin in the blood has the opposite effect, promoting widespread catabolism, especially of reserve body fat.

<span class="mw-page-title-main">Pancreas</span> Organ of the digestive system and endocrine system of vertebrates

The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e., it has both an endocrine and a digestive exocrine function. 99% of the pancreas is exocrine and 1% is endocrine. As an endocrine gland, it functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin and pancreatic polypeptide. As a part of the digestive system, it functions as an exocrine gland secreting pancreatic juice into the duodenum through the pancreatic duct. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach; and digestive enzymes, which break down carbohydrates, proteins and fats in food entering the duodenum from the stomach.

The following is a glossary of diabetes which explains terms connected with diabetes.

<span class="mw-page-title-main">Beta cell</span> Type of cell found in pancreatic islets

Beta cells (β-cells) are specialized endocrine cells located within the pancreatic islets of Langerhans responsible for the production and release of insulin and amylin. Constituting ~50–70% of cells in human islets, beta cells play a vital role in maintaining blood glucose levels. Problems with beta cells can lead to disorders such as diabetes.

<span class="mw-page-title-main">Glycogen</span> Glucose polymer used as energy store in animals

Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. It is the main storage form of glucose in the human body.

<span class="mw-page-title-main">Glucagon</span> Peptide hormone

Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises the concentration of glucose and fatty acids in the bloodstream and is considered to be the main catabolic hormone of the body. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers extracellular glucose. It is produced from proglucagon, encoded by the GCG gene.

<span class="mw-page-title-main">Blood sugar level</span> Concentration of glucose present in the blood (Glycaemia)

The blood sugar level, blood sugar concentration, blood glucose level, or glycemia is the measure of glucose concentrated in the blood. The body tightly regulates blood glucose levels as a part of metabolic homeostasis.

Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms.

<span class="mw-page-title-main">Glucokinase</span> Enzyme participating to the regulation of carbohydrate metabolism

Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver and pancreas of humans and most other vertebrates. In each of these organs it plays an important role in the regulation of carbohydrate metabolism by acting as a glucose sensor, triggering shifts in metabolism or cell function in response to rising or falling levels of glucose, such as occur after a meal or when fasting. Mutations of the gene for this enzyme can cause unusual forms of diabetes or hypoglycemia.

<span class="mw-page-title-main">Alpha cell</span> Glucagon secreting cell

Alpha cells (α-cells) are endocrine cells that are found in the Islets of Langerhans in the pancreas. Alpha cells secrete the peptide hormone glucagon in order to increase glucose levels in the blood stream.

<span class="mw-page-title-main">Trehalose</span> Chemical compound

Trehalose is a sugar consisting of two molecules of glucose. It is also known as mycose or tremalose. Some bacteria, fungi, plants and invertebrate animals synthesize it as a source of energy, and to survive freezing and lack of water.

<span class="mw-page-title-main">Gastric inhibitory polypeptide</span> Mammalian protein found in Homo sapiens

Gastric inhibitory polypeptide(GIP), also known as glucose-dependent insulinotropic polypeptide, is an inhibiting hormone of the secretin family of hormones. While it is a weak inhibitor of gastric acid secretion, its main role, being an incretin, is to stimulate insulin secretion.

<span class="mw-page-title-main">Reactive hypoglycemia</span> Medical condition

Reactive hypoglycemia, postprandial hypoglycemia, or sugar crash is a term describing recurrent episodes of symptomatic hypoglycemia occurring within four hours after a high carbohydrate meal in people with and without diabetes. The term is not necessarily a diagnosis since it requires an evaluation to determine the cause of the hypoglycemia.

Enteroglucagon is a peptide hormone derived from preproglucagon. It is a gastrointestinal hormone, secreted from mucosal cells primarily of the colon and terminal ileum. It consists of 37 amino acids. Enteroglucagon is released when fats and glucose are present in the small intestine; which decrease the motility to allow sufficient time for these nutrients to be absorbed.

<span class="mw-page-title-main">Type 1 diabetes</span> Form of diabetes mellitus

Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when pancreatic cells are destroyed by the body's immune system. In healthy persons, beta cells produce insulin. Insulin is a hormone required by the body to store and convert blood sugar into energy. T1D results in high blood sugar levels in the body prior to treatment. Common symptoms include frequent urination, increased thirst, increased hunger, weight loss, and other complications. Additional symptoms may include blurry vision, tiredness, and slow wound healing. While some cases take longer, symptoms usually appear within weeks or a few months.

<span class="mw-page-title-main">Glucagon-like peptide-1 receptor</span> Receptor activated by peptide hormone GLP-1

The glucagon-like peptide-1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by the gene GLP1R, which is present on chromosome 6. It is a member of the glucagon receptor family of GPCRs. GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1. In the TMD domain there is a fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism.

The insulin transduction pathway is a biochemical pathway by which insulin increases the uptake of glucose into fat and muscle cells and reduces the synthesis of glucose in the liver and hence is involved in maintaining glucose homeostasis. This pathway is also influenced by fed versus fasting states, stress levels, and a variety of other hormones.

Heterocrine glands are the glands which function as both exocrine gland and endocrine gland. These glands exhibit a unique and diverse secretory function encompassing the release of proteins and non-proteinaceous compounds, endocrine and exocrine secretions into both the bloodstream and ducts respectively. This duality allows them to serve crucial roles in regulating various physiological processes and maintaining homeostasis. These include the gonads, pancreas and salivary glands.

References

  1. 1 2 3 Aronoff SL, Berkowitz K, Shreiner B, Want L (2004). "Glucose metabolism and regulation: Beyond insulin and glucagon". Diabetes Spectrum. 17 (3): 183–90. doi:10.2337/diaspect.17.3.183.
  2. ↑ BOLIE, VW (September 1961). "Coefficients of normal blood glucose regulation". Journal of Applied Physiology. 16 (5): 783–8. doi:10.1152/jappl.1961.16.5.783. PMID   13870789.
  3. ↑ Matthews, DR; Hosker, JP; Rudenski, AS; Naylor, BA; Treacher, DF; Turner, RC (July 1985). "Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man". Diabetologia. 28 (7): 412–9. doi: 10.1007/BF00280883 . PMID   3899825. S2CID   24872571.
  4. ↑ Bergman, RN (2020). "Origins and History of the Minimal Model of Glucose Regulation". Frontiers in Endocrinology. 11: 583016. doi: 10.3389/fendo.2020.583016 . PMC   7917251 . PMID   33658981.
  5. ↑ Dietrich, JW; Dasgupta, R; Anoop, S; Jebasingh, F; Kurian, ME; Inbakumari, M; Boehm, BO; Thomas, N (21 October 2022). "SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function". Scientific Reports. 12 (1): 17659. Bibcode:2022NatSR..1217659D. doi:10.1038/s41598-022-22531-3. PMC   9587026 . PMID   36271244. S2CID   253041870.
  6. ↑ Gandasi, Nikhil R.; Yin, Peng; Omar-Hmeadi, Muhmmad; Laakso, Emilia Ottosson; Vikman, Petter; Barg, Sebastian (2018-02-06). "Glucose-Dependent Granule Docking Limits Insulin Secretion and Is Decreased in Human Type 2 Diabetes". Cell Metabolism. 27 (2): 470–478.e4. doi: 10.1016/j.cmet.2017.12.017 . ISSN   1550-4131. PMID   29414688.
  7. ↑ Ebey Soman, Scienceray, Regulation of Glucose by Insulin Archived July 16, 2011, at the Wayback Machine , May 4, 2009. Retrieved November 1, 2009.
  8. ↑ Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, Saha PK, Del Solar M, Zhu B, York B, Sarkar P, Rendon DA, Gaber MW, LeMaire SA, Coselli JS, Milewicz DM, Sutton VR, Butte NF, Moore DD, Chopra AR (April 2016). "Asprosin, a Fasting-Induced Glucogenic Protein Hormone". Cell. 165 (3): 566–79. doi:10.1016/j.cell.2016.02.063. PMC   4852710 . PMID   27087445.
  9. ↑ Shukla, E; Thorat, LJ; Nath, BB; Gaikwad, SM (April 2015). "Insect trehalase: physiological significance and potential applications". Glycobiology. 25 (4): 357–67. doi:10.1093/glycob/cwu125. PMID   25429048.
  10. ↑ Becker, A; Schlöder, P; Steele, JE; Wegener, G (15 May 1996). "The regulation of trehalose metabolism in insects". Experientia. 52 (5): 433–9. doi:10.1007/BF01919312. PMID   8706810.
  11. ↑ Tellis, MB; Kotkar, HM; Joshi, RS (17 May 2023). "Regulation of trehalose metabolism in insects: from genes to the metabolite window". Glycobiology. 33 (4): 262–273. doi:10.1093/glycob/cwad011. PMID   36762907.
  12. ↑ Nässel, DR; Vanden Broeck, J (January 2016). "Insulin/IGF signaling in Drosophila and other insects: factors that regulate production, release and post-release action of the insulin-like peptides". Cellular and Molecular Life Sciences. 73 (2): 271–90. doi:10.1007/s00018-015-2063-3. PMC   11108470 . PMID   26472340.
  13. ↑ Nässel, DR; Zandawala, M (July 2022). "Endocrine cybernetics: neuropeptides as molecular switches in behavioural decisions". Open Biology. 12 (7): 220174. doi:10.1098/rsob.220174. PMC   9326288 . PMID   35892199.
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