The insulin concentration in blood increases after meals and gradually returns to basal levels during the next 1–2 hours. However, the basal insulin level is not stable. It

oscillates Oscillation is the repetitive or periodic variation, typically in time, of some measure about a central value (often a point of equilibrium) or between two or more different states. Familiar examples of oscillation include a swinging pendulum ...

with a regular period of 3-6 min. After a meal the amplitude of these oscillations increases but the periodicity remains constant. English Summary: https://lakartidningen.se/klinik-och-vetenskap-1/2007/08/insulinoscillationer-ndash-en-kliniskt-betydelsefull-rytmik/#eng The oscillations are believed to be important for insulin sensitivity by preventing

downregulation In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pr ...

insulin receptor The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose ho ...

s in target cells. Such downregulation underlies insulin resistance, which is common in

type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...

. It would therefore be advantageous to administer insulin to

diabetic Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

patients in a manner mimicking the natural oscillations. The insulin oscillations are generated by pulsatile release of the hormone from the

pancreas 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 en ...

. Insulin originates from beta cells located in the

islets of Langerhans The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of ...

. Since each islet contains up to 2000 beta cells and there are one million islets in the pancreas it is apparent that pulsatile secretion requires sophisticated synchronization both within and among the islets of Langerhans.

Mechanism

Pulsatile insulin secretion from individual beta cells is driven by oscillation of the calcium concentration in the cells. In beta cells lacking contact, the periodicity of these oscillations is rather variable (2-10 min). However, within an islet of Langerhans the oscillations become synchronized by electrical coupling between closely located beta cells that are connected by

gap junctions Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regula ...

, and the periodicity is more uniform (3-6 min). Pulsatile insulin release from the entire pancreas requires that secretion is synchronized between 1 million islets within a 25 cm long organ. Much like the

cardiac pacemaker 350px, Image showing the cardiac pacemaker or SA node, the primary pacemaker within the electrical_conduction_system_of_the_heart">SA_node,_the_primary_pacemaker_within_the_electrical_conduction_system_of_the_heart. The_muscle_contraction.htm ...

, the pancreas is connected to cranial nerve 10, and others, but the oscillations are accomplished by intrapancreatic neurons and do not require neural input from the brain. It is not entirely clear which neural factors account for this synchronization but ATP as well as the gasses NO and CO may be involved. The effect of these neural factors is to induce sudden dramatic elevation of calcium in the cytoplasm by releasing calcium from the endoplasmic reticulum (ER) of the beta cells. This elevation results in release of ATP from the beta cells. The released ATP in turn binds to

receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

on neighbouring beta cells leading to a regenerative wave of rapid calcium elevation among the cells within the islet. This signal is believed to entrain pulsatile insulin release from the islets into a common pancreatic rhythm.

Clinical significance

The insulin oscillations are particularly pronounced in the portal vein delivering blood from the pancreas to the liver, which is a major insulin target. Disturbances of the insulin oscillations occur early in type 2 diabetes and may contribute to insulin resistance. Pulsatile insulin delivery to the portal vein or

islet cell transplantation Islet transplantation is the transplantation of isolated islets from a donor pancreas into another person. It is an experimental treatment for type 1 diabetes mellitus. Once transplanted, the islets begin to produce insulin, actively regulating th ...

to the liver of diabetic patients are therefore attractive therapeutic alternatives.

References

{{reflist Oscillation Endocrine system

Mechanism

Clinical significance

Further reading

See also

References