Mechanism of insulin secretion

Mechanisms of Insulin Secretion The beta cells have a large number of glucose transporters (GLUT-2) that permit a rate of glucose influx that is propor-tional to the blood concentration in the physiologic range. Mechanisms of Insulin Secretion

Mechanisms of Insulin Secretion - BrainKar

  1. The mechanism of insulin secretion* S. L. Howell Department of Physiology, Queen Elizabeth College, University of London, London, UK There had been a number of attempts before 1889 to assess the effects of pancreatectomy on blood glucose regulation, but the results had been controversial, prob-.
  2. Many years studying this amplifying process have shaped our current understanding of β cell stimulus-secretion coupling; yet, the exact mechanisms of amplification have been elusive. Recent studies utilizing metabolomics, computational modeling, and animal models have progressed our understanding of the metabolic amplifying pathway of insulin.
  3. ating for ALA and anti-inflammatory effects for DHA. Modifying both GLP-1 release and the actions of adipokines by n-3 PUFAs could lead to additive improvements in both insulin secretion and sensitivity
  4. ute of stimulation (Civelek et al., 1996) (Fig. 1, #1)
  5. o acids can augment glucose-induced insulin secretion
  6. Insulin is secreted in primarily in response to elevated blood concentrations of glucose. This makes sense because insulin is in charge of facilitating glucose entry into cells

Insulin secretion is governed by the interaction of nutrients, hormones, and the autonomic nervous system. Glucose, as well as certain other sugars metabolized by islets, stimulates insulin release Kisspeptin stimulation of insulin secretion: mechanisms of action in mouse islets and rats Diabetologia. 2009 May;52(5):855-62. doi: 10.1007/s00125-009-1283-1. Epub 2009 Feb 17. Authors J E Bowe 1 , A J King, J S Kinsey-Jones, V L Foot, X F Li, K T O'Byrne, S J Persaud, P M Jones. Affiliation 1 Division of.

Mechanism of INSULIN Secretion (ANIMATION)Doc OTEP's Studio - Recording and Animatio Mechanisms of Insulin Secretion The secretion of insulin from pancreatic beta cells is a complex process involving the integration and interaction of multiple external and internal stimuli. Thus, nutrients, hormones, neurotransmitters, and drugs all activate -- or inhibit -- insulin release The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis. Decreased or absent insulin activity results in diabetes mellitus, a condition of high blood sugar level (hyperglycaemia). There are two types of the disease This chapter describes the mechanism of insulin secretion. D-glucose is the major physiological initiator of insulin release This video dissects the mechanism by which the Pancreatic β-cells sense blood glucose levels and secrete a proportional amount of insulin through negative fe..

Mechanisms of insulin secretion in malnutrition

Glucose-stimulated Insulin Secretion: The Hierarchy Of Its Multiple Cellular And Subcellular Mechanisms. Beta cells Confocal microscopy Connexin Cx36 Exocytosis Glucose Heterogeneity Insulin release Pancreatic islets Secretory granules Stimulus-secretion coupling Glucose-stimulated insulin secretion is the hallmark of a differentiated beta cell, and the early loss of this feature is a. Insulin secretion: mechanism of the stimulation by glucose - Volume 8 Issue 1. Skip to main content Accessibility help We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings

Insulin secretion is controlled by β-cell electrical activity. As in neurons and many other endocrine cells, electrical signals play a central role in the regulation of secretion. In 1968, Dean and Matthews demonstrated that the β-cell is electrically excitable ( 2 ). When the extracellular glucose concentration is elevated from the basal. The insulin content of the blood of the pancreatico-duodenal vein and femoral artery of dogs (obtained by the authors' method of angiostomy) was determined by its effect on the blood sugar of mice. Increase of Mood sugar produced by injection of glucose or adrenaline led to an increase of insulin in the pancreatico-duodenal vein: the secretion of insulin was inhibited by blockage of the vagus.. Oncogenic transformation and the reductions of insulin secretion and proliferative calcium dependence during repeated passage of pancreatic islet cells in vitro Cancer Letters, Vol. 14, No. 2 Effects of 4-aminopyridine on insulin secretion and plasma glucose levels in intact and adrenalectomized-chemically symphathectomized mic Key Terms. insulin: A polypeptide hormone that regulates carbohydrate metabolism.; glycogen: A polysaccharide that is the main form of carbohydrate storage in animals and also converts to glucose as needed.; glucagon: A hormone, produced by the pancreas, that opposes the action of insulin by stimulating the production of sugar.; Glucagon and insulin are peptide hormones secreted by the. Sulfonylureas stimulate insulin secretion from pancreatic β-cells and are widely used to treat type 2 diabetes. Their principal target is the ATP-sensitive potassium (K ATP) channel, which plays a major role in controlling the β-cell membrane potential.Inhibition of K ATP channels by glucose or sulfonylureas causes depolarization of the β-cell membrane; in turn, this triggers the opening of.

Mechanisms of the amplifying pathway of insulin secretion

Animation: Insulin Secretion And Sulfonylureas Mechanism Of Action. Sulfonylureas are the most widely prescribed drugs in the treatment of type II diabetes mellitus. The initial sulfonylureas were introduced nearly 50 years ago and were derivatives of the antibacterial sulfonamides A well-known effect of insulin is to decrease the concentration of glucose in blood, which should make sense considering the mechanisms described above. Another important consideration is that, as blood glucose concentrations fall, insulin secretion ceases

Clinical Trials, Triumphs, and Tribulations of Glucagon

Mechanisms of enhanced insulin secretion and sensitivity

Insulin secretion in vivo follows a characteristic biphasic time course: an initial component, which develops rapidly but only lasts a few minutes (1st phase), is followed by a slowly developing but sustained component (2nd phase) (Curry et al. 1968).Type-2 diabetes is associated with complete loss of 1st phase secretion and strong reduction of 2nd phase release (Hosker et al. 1989) This response of insulin secretion to an elevated blood glucose concentration provides an extremely important feedback mechanism for regulating blood glucose concentration. That is, any rise in blood glucose increases insulin secretion, and the insulin in turn increases transport of glucose into liver, muscle, and other cells, thereby reducing. Pancreatic 5-HT is co-secreted from β cells where it acts at 5-HT 1A Rs, 5-HT 1F Rs and 5-HT 2B Rs to influence insulin secretion. The mechanisms through which 5-HT modulates insulin sensitivity and insulin release are still not well understood and provide an exciting opportunity for future research. ACKNOWLEDGEMENTS Insulin secretion mechanism is a common example of signal transduction pathway mechanism. Insulin is produced by the pancreas in a region called Islets of Langerhans. In the islets of Langerhans, there are beta-cells, which are responsible for production and storage of insulin. Insulin is secreted as a response mechanism for counteracting the.

Regulation of Insulin Synthesis and Secretion and

This effect on insulin secretion occurs in the fed state (10). Mechanisms explaining glucagon secretion are not as well understood as those of insulin secretion, although the direct effect of reduced glucose on cAMP (111), and the sodium-glucose cotransporters (SGLT) are thought to play a role in a-cell glucose transport (3) Insulin Regulation. The primary physiological variable which controls insulin release from beta cells is the concentration of blood glucose. However, a variety of hormones can modulate beta cell-mediated release of insulin allowing fine-tuning of insulin levels to physiological demands. The molecular mechanism by which beta cells sense and. Handbook of Diabetes, 4th Edition, Excerpt #4: Normal Physiology of Insulin Secretion and Action. Insulin is synthesized in and secreted from the β-cells within the islets of Langerhans in the pancreas. The normal pancreas has about 1 million islets, which constitute about 2-3% of the gland's mass A role for the arcuate nucleus in insulin secretion is also supported by studies showing that the intracerebroventricular administration of NPY, normally synthesized and secreted by arcuate neurons, rapidly induces insulin secretion, through mechanisms that can be suppressed by vagotomy 29, 30 INSULIN AND INSULIN ANALOGS Mechanism of action • Exogenous insulin is administered to replace absent insulin secretion in type1 diabetes or to supplement insufficient insulin secretion in type 2 diabetes. Pharmacokinetics and fate • Human insulin is produced by recombinant DNA technology using strains of Escherichia coli or yeast that are genetically altered to contain the gen

Frontiers | Diabetes Secondary to Acromegaly

Insulin and glucagon work in what's called a negative feedback loop. During this process, one event triggers another, which triggers another, and so on, to keep your blood sugar levels balanced (A) Insulin secretion in basal glucose (2.8 mM) was determined in islets incubated for 1 h with different concentrations of H 2 O 2. An increase in insulin secretion in basal glucose was observed at 100 μM H 2 O 2. (B) Insulin secretion in stimulatory glucose (16.7 mM) in islets incubated for 1 h with different concentrations of H 2 O 2. Mean. Mechanisms of the Age-Associated Deterioration in Glucose Tolerance Contribution of Alterations in Insulin Secretion, Action, and Clearance Rita Basu,1 Elena Breda,5 Ann L. Oberg,2 Claudia C. Powell,2 Chiara Dalla Man,5 Ananda Basu,1 Janet L. Vittone,3 George G. Klee,4 Puneet Arora,1 Michael D. Jensen,1 Gianna Toffolo,5 Claudio Cobelli,5 and Robert A. Rizza1 Glucose tolerance decreases with age Other products released from β-cells during insulin secretion, including zinc and GABA, are reported to dampen glucagon secretion by a paracrine mechanism 89,90, although the physiological.

Insulin Synthesis and Secretio

The mechanism of insulin secretion The mechanism of insulin secretion Howell, S. 1984-05-01 00:00:00 Diabetologia (1984) 26:319-327 Diabetologia 9 Springer-Verlag 1984 Review article S. L. Howell Department of Physiology, Queen Elizabeth College, University of London, London, UK There had been a number of attempts before 1889 to assess the effects of pancreatectomy on blood glucose regulation. Patient was educated on Tradjenta and its mechanism of action as follows: Rise in the blood sugars stimulates release of a natural hormone in the human body, called Incretin. Incretin brings about the secretion of insulin from the pancreas and insulin helps with uptake of glucose by the tissues and lowers the blood glucose. As [ Mechanisms of glucose-stimulated insulin secretion and abnormalities in diabetes. Glucose and other nutrients regulate insulin secretion by the pancreatic beta cell. Glucose is transported by a glucose transporter (GLUT1 and/or GLUT2 in humans, GLUT2 in rodents); subsequent glucose metabolism by the beta cell alters ion channel activity, leading to insulin secretion The proposed mechanisms for these abnormalities are a decrease in pancreatic β cell mass, leading to hypoinsulinemia, and decreased adiponectin, causing insulin resistance. Another group demonstrated that disruption of the IR in osteoblasts was sufficient to reduce osteocalcin and produce similar metabolic changes ( 14 ) Although insufficient insulin secretion is the primary cause of hyperglycaemia in diabetes it has become increasingly clear that hypersecretion of glucagon contributes 120 and may even be a prerequisite for development of the disease. 48 β-Cell failure is probably the ultimate cause of glucagon hypersecretion in hyperglycaemia because of.

Insulin Secretion - an overview ScienceDirect Topic

INTEGRATIVE PHYSIOLOGY An Osteoblast-dependent Mechanism Contributes to the Leptin Regulation of Insulin Secretion Eiichi Hinoi,a Nan Gao,b Dae Young Jung,c Vijay Yadav,a Tatsuya Yoshizawa,a Daisuke Kajimura,a Martin G. Myers, Jr.,d Streamson C. Chua, Jr.,e Qin Wang,f Jason K. Kim,c Klaus H. Kaestner,b and Gerard Karsentya a Department of Genetics and Development, College of Physicians and. Insulin is a peptide hormone produced by beta cells within the pancreas. It is responsible for regulating movement of glucose from the blood into cells. This article will consider the structure of insulin, how it is synthesised and secreted, its actions on the body and clinical conditions that are associated with faults in its production Pancreatic β cells secrete insulin, the body's only hormone capable of lowering plasma glucose levels. Impaired or insufficient insulin secretion results in diabetes mellitus. The β cell is electrically excitable; in response to an elevation of glucose, it depolarizes and starts generating action potentials. The electrophysiology of mouse β cells and the cell's role in insulin secretion. This proposal stems from our recent discovery of a mechanism that regulates secretion at low glucose without compromising glucose-stimulated insulin secretion, which has the potential to not only treat T2D but also reverse some of the driving forces that lead to ?-cell exhaustion and initiation of insulin therapy in patients The intracellular P i level and the ammonia production rate were doubled, while insulin secretion was decreased 10-fold, upon switching from 16 mM to 0 mM glucose. The implications of these findings in the context of pancreatic β cell biochemistry and the mechanism of the 'Fuel Hypothesis' are discussed

Feedback mechanism to protect against excessive FA mobilization and ketosis. taste or smell of food increases insulin secretion by Ach or VIP release, which causes vagal nerve stimulation of pancreas to secrete insulin and promote glucose uptake by live metabolic facets of insulin secretion and action that are pertinent to the development of DM. Metabolic regulation of b-cell insulin secretion Biochemical mechanisms of insulin secretion Insulin exocytosis is a highly controlled process, and many factors actively promote insulin release (refer to Fu et al. (2013) for more detail)

In this model, insulin resistance represents a cellular protective mechanism that is aimed to control the ATP stress response in the muscle and liver. Insulin-sensitizing agents rescue the tissue. This study aimed at elucidating the mechanism by which ISCs regulate insulin secretion from Min6 cells via the Wnt5a protein. Methods . Glucose-stimulated insulin secretion (GSIS) from Min6 cells was examined by estimating the insulin levels in response to high glucose challenge after culture with ISC supernatant or exogenous Wnt5a Because little is known regarding the signaling mechanisms involved in estradiol-mediated insulin secretion, we investigated the role of the G protein-coupled receptor 30, now designated G protein-coupled estrogen receptor (GPER), in activating signal transduction cascades in β-cells, leading to secretion of insulin

Kisspeptin stimulation of insulin secretion: mechanisms of

Mechanism of Increased Glucose-Induced Insulin Secretion from Pancreatic Islets Isolated from Dexamethasone Treated Rats Is Proximal to Influx of Intracellular Calcium Increased insulin secretion oc Increased insulin secretion occurs in response to insulin resistance. Glucocorticoids are known to cause insulin resistance and hyperinsulinemia Pancreatic Thyrotropin Releasing Hormone and Mechanism of Insulin Secretion. October 2018; Cellular Physiology and Biochemistry 50(1):378-384; DOI:10.1159/000494013. Abstract. The paired box 6 (PAX6) transcription factor is crucial for normal pancreatic islet development and function. Heterozygous mutations of PAX6 are associated with impaired insulin secretion and early-onset diabetes mellitus in humans. However, the molecular mechanism of PAX6 in controlling insulin secretion in human beta cells and its pathophysiological role in type 2 diabetes (T2D.

Mechanisms by which various classes of extracellular signals regulate insulin secretion are discussed regarding their cellular and molecular actions. Under physiological circumstances, the small postprandial changes in plasma glucose concentrations (∼4.4-6.6 mM) primarily serve as a conditional modifier of insulin secretion and dramatically alter the responsiveness of islets to a. The loss of glucose-stimulated insulin secretion from these β cells marks the onset of T2D. In a study published online Sept. 24 in the journal Cell Reports , the research team found a significant increase in the purine/nucleotide metabolic pathway intermediate adenylosuccinate (S-AMP) in islets stimulated with glucose New Zealand research revealing a new mechanism for how glucose stimulates insulin secretion may provide a new explanation for how a gene that makes people more susceptible to diabetes - called. Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic beta-cells. Endocrinology . 2011 Aug. 152(8):3030-9. [Medline]

The dysfunction of pancreatic insulin secretion is an important pathophysiological basis of diabetes mellitus and the active ingredients extracted from plants have the ability to regulate insulin secretion in the body. These active ingredients mainly include polysaccharides, flavonoids, terpenes, polyphenols, alkaloids and so on. Compared with oral hypoglycemic drugs on insulin secretion, the. The response of BRIN-BD11 cells to glucose and amino acids indicates that this is a useful cell line for future research on the mechanisms of nutrient regulation of insulin secretion. Journal of Endocrinology (1996) 151, 349-35 Mechanisms of Insulin Secretion . Insulin is produced in the pancreas and the Brockmann body (in some fish), and released when any of several stimuli are detected. These stimuli include ingested protein and glucose in the blood produced from digested food.[3] Carbohydrates can be polymers of simple sugars or the simple sugars themselves Insulin-like signaling integrates the storage and release of nutrients with somatic growth during development and in adult life. It is a feature of all metazoans, revealing a common mechanism used by animals to integrate metabolism and growth with environmental signals. 1, 2 Lower animals have a wide array of insulin-like peptides—seven in fruit flies and 38 in Caenorhabditis elegans—that. Incretins are secreted into the blood stream, reach the beta cells, and enhances glucose-dependent insulin secretion of beta cells => It is this mechanism that is the focus of paper 3 - how exactly does this work and what exactly happens when patients have insulin resistance and diabete

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Mechanism of INSULIN Secretion (ANIMATION) - YouTub

Viewed 1k times. 2. Is there any known mechanism by which hypokalemia reduces insulin secretion? This video explains a mechanism, but its inherently wrong because ATP dependent K+ channels will allow movement of K+ from inside of cell to outside. human-biology biochemistry physiology pharmacology diabetes-mellitus Animation depicting how sulfonylureas enhance insulin secretion by binding to specific beta cell receptors. Download availabl Insulin Test of Gastric Secretion: Insulin reduces blood sugar which in its turn, stimulates vagus and thereby excites gastric secretion. A positive insulin test is proof of the presence of intact vagal fibres but a negative result is less conclusive since some subjects with intact vagi fail to secrete in response to insulin Insulin is not secreted if the blood glucose concentration is ≤ 3.3 mmol/l, but is secreted in increasing amounts as glucose concentrations increase beyond this threshold. 14 Postprandially, the secretion of insulin occurs in two phases: an initial rapid release of preformed insulin, followed by increased insulin synthesis and release in.

Regulation of Insulin Secretion - Medscap

1-30 increases insulin secretion in perfused mouse pancreata, and immunoneutralization of GIP decreased glucose-stimulated insulin secretion in isolated mouse islets, consistent with the local release of an insulinotropic GIP peptide from a cells (Fujita et al., 2010). Ectopic expression of biologi Insulin and Potassium. Insulin has a number of actions on the body besides lowering your blood glucose levels. Insulin suppresses the breakdown and buildup of glycogen, which is the storage form of glucose, it blocks fat metabolism and the release of fatty acids, and it puts potassium into the cells by activating the sodium-potassium cellular channels

Thus, the development of type 2 diabetes is usually characterized by 2 abnormalities: impaired insulin action and deficient insulin secretion. Both impairments are made worse by hyperglycemia mechanisms of insulin secretion. A number of studies have shown that changes in the intracellular free Ca-^ concentration, [Ca^^];, play a central role in the regulation of insulin secretion in pancreatic beta-cells (Ashcraft, 1994). Insulin secretion is triggered by a rise o

Insulin - Wikipedi

Mechanism of Action. Glipizide is in the sulfonylurea class of antihyperglycemic medication. The mechanism of action is the stimulation of insulin secretion from the beta cells of pancreatic islet tissue and is thus dependent on functioning beta cells in the pancreatic islets. Peak plasma concentrations occur 1 to 3 hours after a single oral dose The insulin secreting porosome is a supramolecular lipo-protein complex that measures roughly 100 - 120 nm in diameter. Porosomes allow transient fusion of insulin secretory granules to the cell plasma membrane and mediates partial release of secretory contents. Post secretion, the secretory granule reseals and re-enters to the cell interior Mechanism of Action Metformin is an antihyperglycemic agent, which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. insulin secretion remains unchanged while fasting insulin levels and daylong plasma insulin response may actually decrease. Pharmacokinetic The discovery of insulin and its receptor was essential to understand the mechanisms controlling glucose homeostasis and the pathogenesis of type 2 diabetes defined by defective insulin secretion. Whereas biguanides, glitazones, sulfonylureas and meglitinides affect insulin sensitivity or secretion, alpha-glucosidase inhibitors have no such effect. Instead, they work by slowing carbohydrate metabolism throughout the gastrointestinal tract - an effect achieved by decreasing carbohydrate enzyme production


The pancreas secretes insulin and glucagon. Both hormones work in balance to play a vital role in regulating blood sugar levels. If the level of one hormone is higher or lower than the ideal range. T2 - Pharmacologic Mechanisms Impacting Both Insulin Resistance and Insulin Secretion Leading to Glucose Dysregulation and Diabetes Mellitus. AU - Chakkera, Harini M. AU - Kudva, Yogish C. AU - Kaplan, B. PY - 2017/1/1. Y1 - 2017/1/ To address the mechanism of sulfonylurea action, we employed a recently validated canine model with a portal vein sampling catheter and flow probe to measure pulsatile insulin secretion in vivo directly in response to tolbutamide infusion or ingestion

Insulin Synthesis and Secretion - YouTubeNonpeptidic glucagon-like peptide 1 receptor agonists: A

Pathogenetic mechanisms of impaired glucose tolerance and type II diabetes in African-Americans: The significance of insulin secretion, insulin sensitivity, and glucose effectiveness Article. Overview Identifiers Additional Document Info View All Overview. fiu authors . Gaillard, Trudy. For studies of insulin secretion from ZDF islets, cells were washed with PBS and preincubated in HBSS containing 3 m m glucose for 1 h. Insulin secretion was then measured with the same static incubation protocol as described for 832/13 cells, using two uniformly sized islets/condition in triplicate and exposed to 3 or 16.7 m m glucose Mechanism of Fatty Acid-induced Impairment of Glucose-simulated Insulin Secretion - Effect of Buphenyl. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government

Since insulin secretion can be rapidly tuned by changes in pancreatic microcirculation, scientists at the Stockholm South Hospital Diabetes Research Center, Karolinska Institutet, evaluated the. mechanisms by which Mg2+ contributes to IR are still under discussion. Currently, the strongest line of evidence supports the effects of MgD on insulin secretion, insulin sensitivity, systemic inflammatory response, and the activity of certain key Mg2+-dependent enzymes of carbohydrate and energy metabolism. 2.1. Effects of MgD on Insulin.

Is the Diminished Incretin Effect in Type 2 Diabetes Just

Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin glargine is a long-acting insulin analogue with a flat and predictable action profile. It is used to mimic the basal levels of insulin in diabetic individuals. Mechanism of action Pancreatic islet β-cell dysfunction is characterized by defective glucose-stimulated insulin secretion (GSIS) and is a predominant component of the pathophysiology of diabetes. Imeglimin, a novel first-in-class small molecule tetrahydrotriazine drug candidate, improves glycemia and GSIS in preclinical models and clinical trials in patients with Type 2 diabetes; however, the mechanism by which. Regulation of insulin secretion. Pancreatic beta cells integrate signals from several metabolites and hormones to control the secretion of insulin. In general, glucose triggers insulin secretion while other factors can amplify or inhibit the amount of insulin secreted in response to glucose. Factors which increase insulin secretion include the.

Brain IL-6—Where Amylin and GLP-1 Antiobesity SignalingThe challenge of managing coexistent type 2 diabetes and

Insulin, hormone that regulates the level of sugar in the blood and that is produced by the beta cells of the islets of Langerhans in the pancreas.Insulin is secreted when the level of blood glucose rises—as after a meal. When the level of blood glucose falls, secretion of insulin stops, and the liver releases glucose into the blood. Insulin was first reported in pancreatic extracts in 1921. FIGURE 8 Betagranin inhibits the insulin secretion in the perfused pancreas. A, in the perfused rat pancreas, 10 n m betagranin rapidly and reversibly inhibited insulin secretion in response to both 5.6 and 16.7 m m glucose. Data are mean ± S.E. (n = 5). B, quantitative evaluation of the effect by measuring the areas under the curve synthesis and secretion o The decrease in insulin secretion along with a decrease in amylin secretion leads to an increase in glucagon Increased glucagon stimulates glycogenolysis and gluconeogenesis, resulting in hyperglycemia.-Type 2 Diabetes o Genetic abnormalities combined with environmental influences result in the basic pathophysiologic mechanisms of type 2 diabetes, which are insulin. amplification mechanisms of insulin secretion, notably in incretin- (GLP-1- and GIP-) and metabotropic receptor signaling (71,218). We found that insulin secretion stimulated by branched-chain keto acids (BCKAs) (194) and partly by fatty acids (FAs) (98,103) essentially relies on mitochondrial retrograde redox signaling 4.4.1. Stimulation of Insulin Secretion by Vitamin D and Calcium. There is evidence that vitamin D may stimulate pancreatic insulin secretion directly. Vitamin D exerts its effects through nuclear vitamin D receptors . The stimulatory effects of vitamin D on insulin secretion may only manifest when calcium levels are adequate