Turkiye Klinikleri Journal of Health Sciences

.: REVIEW
İnsülinin Üretim-Salgı Mekanizması ve Sekresyonunun Düzenlenmesi
Regulation of Insulin Secretion and Mechanism of Production-Secretion
Merve ÖZTAĞa,b, Angelos K. SIKALIDISa
aBeslenme ve Diyetetik Bölümü, Istanbul Yeni Yüzyıl Üniversitesi, Sağlık Bilimleri Fakültesi,
bBeslenme ve Diyetetik Bölümü, Marmara Üniversitesi, Sağlık Bilimleri Fakültesi, İstanbul, TÜRKİYE
Turkiye Klinikleri J Health Sci. 2018;3(3):263-70
doi: 10.5336/healthsci.2017-58737
Article Language: TR
Full Text
ÖZET
İnsülin; çeşitli işlevleri gören ve majör işlev bakımından kas ve adipoz doku olarak adlandırılan, periferik dokuların glukoz klerensini gerçekleştiren bir polipeptit hormondur. Langerhans adacıklarındaki pankreatik β hücrelerinden, proteolitik bölünmeyi içeren kapsamlı bir posttranslasyonel modifikasyon yoluyla üretilmektedir. Üretilen insülin, salgılanana kadar β-hücrelerinde bulunan insülin içeren granüllerde bulunmaktadır. İnsülinin üretimi ve salgılanması tamamen bağımsız iki süreçtir. İnsülin sekresyon mekanizması için fikir birliği; β hücrelerin glukozu alarak glukoliz aracılığı ile son ürün olan piruvata çevrilmesi ve bu ürünün mitokondriye taşınarak trikarboksilik asit döngüsünü besleyen ve indirgeyici ekivalanlar oluşturan elektron taşıma zincirine yönlendirilerek adenozin trifosfat (ATP) üretilmesi ile sonuçlanması şeklindedir. ATP üretimi, sitozoldeki K+ kanallarını kapatarak ATP/adenozin difosfat oranını artırmakta, membrandaki depolarizasyonu ve Ca2+ konsantrasyonunu artırarak insülin salgılanması ile sonuçlanmaktadır. Buna rağmen, sitozoldeki Ca2+'nın tek başına yeterli insülinin salınması için yeterli olmadığı görülmüştür. Diğer metabolitlerin artışı da doğru sinyalleme için gerekli olsa da mitokondriyal Ca2+'nın artırılması gerekmektedir. Süksin seviyelerinin artması, mitokondriyal metabolizma ile ilişkili bir şekilde insülin salınımına neden olur iken, glutamat bağımsız olarak insülin salınımına neden olmaktadır. Bu bulgular, sinyal indüksiyonu için Ca2+ düzeylerinin yeterli miktarda gerekli olmasına rağmen, insülin sekresyonu için diğer sinyalleme mediyatörlerine (metabolitlere) ihtiyaç duyulduğunu göstermektedir. Burada tartışılan glutamatın nasıl işleyeceği konusunda birkaç öneri mevcuttur; ancak kesin etki mekanizmasının anlaşılması ise hâlen zordur.

Anahtar Kelimeler: Diyabet; insülin; Ca2+; glukoz regülasyonu; β-hücre; metabolik regülasyon
ABSTRACT
Insulin is a polypeptide hormone rendering a variety of functions with the major one being glucose clearance by peripheral tissues namely muscle and adipose tissue. It is produced by the pancreatic β-cells in the Langerhans islets through extensive posttranslational modification involving proteolytic cleavage and is stored in insulin containing granules in β-cells until secretion. The production and secretion of insulin are two processes that are highly independent while the consensus for the mechanism of insulin secretion prefigures that β-cells take-up glucose and render it to glycolysis of which the end-product pyruvate is transported into the mitochondria and is fed to the trichloroacetic acid cycle yielding reducing equivalent directed to the electron transport chain and producing adenosine triphosphate (ATP). The production of ATP increases the ATP/adenosine diphosphate ratio in the cytosol closing K+ channels and increasing depolarization of the membrane and Ca2+ concentration which in turn results in insulin secretion. However it has been shown that cytosolic Ca2+ alone does not suffice for adequate insulin release. Increase of mitochondrial Ca2+ is necessitated although increase of other metabolites seems to be necessary for proper signaling as well. Increased levels of succinate induce insulin release in a mitochondrial metabolism associated manner whereas glutamate induces insulin release independently. These findings suggest that even though Ca2+ levels are necessary for signal induction other signaling mediators (metabolites) are required for insulin secretion. Glutamate seems to be participating in the regulation of insulin secretion but the exact mechanism of action still is unclear. In this review we discuss in brief the findings and proposals on how insulin secretion is regulated a process that remains elusive albeit the advances in our understanding of the involved pathways.

Keywords: Diabetes; insülin; Ca2+; glucose regulation; β-cells; metabolic regulation

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30.03.2014

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