Secretagogin Regulates Insulin Signaling by Direct Insulin Binding

Sharma, Anand K.; Khandelwal, Radhika; Kumar, Mahesh; Ram, Nanik; Chidananda, Amrutha H.; Raj, T. Avinash; Sharma, Yogendra

doi:10.1016/j.isci.2019.10.066

Cited by 24 publications

(32 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Secretagogin (SCGN) is predominantly expressed by pancreatic β-cells protecting their normal functions. SCGN also acts as an insulin binding protein to make it more stable, avoid its aggregation, improve its functions and enhance its secretion (90,91). In T2DM patients, due to the islet cell dysfunction and endoplasmic reticulum (ER) stress, serum levels of SCGN are elevated reflecting stress and dysfunctional islet cells (92).…”

Section: Pancreasmentioning

confidence: 99%

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

et al. 2020

View full text Add to dashboard Cite

Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro-and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.

show abstract

Section: Pancreasmentioning

confidence: 99%

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

et al. 2020

View full text Add to dashboard Cite

show abstract

“…With regard to pancreatic islet cells, secretagogin has so far been related to insulin release in loss-of-function studies and the regulation of beta-cell proliferation [ 2 , 9 , 12 , 33 ]. SCGN binds insulin and improves insulin signaling when compared to insulin action alone and, accordingly, dropped over the course of an OGTT in one study [ 13 ]. We were not able to replicate these results in our OGTTs, most probably due to the low number of patients for whom these values were available.…”

Section: Discussionmentioning

confidence: 99%

“…SCGN levels did not differ between women with GDM and NGT in the present cohort. However, SCGN is intrinsically linked to insulin secretion and involved in weight control [ 1 , 13 ]. The pregnant women in both groups displayed similar characteristics in terms of BMI and age.…”

Section: Discussionmentioning

confidence: 99%

“…This trend was visible in both women with NGT and GDM, albeit only significant in NGT. SCGN’s ability to bind insulin [ 13 ] might offer an explanation for the lower values in pregnancy compared to postpartum due to the pregnancy-related hyperinsulinemia. Pregnancy is a state of progressing insulin resistance and hyperinsulinemia to supply the fetus with glucose [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…The exact mechanism of secretagogin’s influence on insulin release has only been understood rather recently and involves SCGN-interacting proteins which are either actin-binding proteins, involved in insulin granule trafficking and exocytosis [ 11 ] or have a regulatory function towards the actin cytoskeleton by facilitating vesicle transport to the periphery during insulin release [ 12 ]. SCGN further binds insulin and improves insulin signaling when compared to insulin action alone by increasing insulin-induced phosphorylation of Akt [ 13 ]. Accordingly, SCGN was recently found to be elevated in patients with type 2 diabetes [ 14 ] and has been related to beta-cell proliferation and insulin secretion [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Secretagogin is Related to Insulin Secretion but Unrelated to Gestational Diabetes Mellitus Status in Pregnancy

Deischinger

Harreiter

Leitner

et al. 2020

JCM

View full text Add to dashboard Cite

Secretagogin (SCGN) is a calcium binding protein related to insulin release in the pancreas. Although SCGN is not co-released with insulin, plasma concentrations have been found to be increased in type 2 diabetes mellitus patients. Until now, no study on SCGN levels in pregnancy or patients with gestational diabetes mellitus (GDM) has been published. In 93 women of a high-risk population for GDM at the Medical University of Vienna, secretagogin levels of 45 GDM patients were compared to 48 women with a normal glucose tolerance (NGT). Glucose tolerance, insulin resistance and secretion were assessed with oral glucose tolerance tests (OGTT) between the 10th and 28th week of gestation (GW) and postpartum. In all women, however, predominantly in women with NGT, there was a significant positive correlation between SCGN levels and Stumvoll first (rp = 0.220, p = 0.032) and second phase index (rp = 0.224, p = 0.028). SCGN levels were not significantly different in women with NGT and GDM. However, SCGN was higher postpartum than during pregnancy (postpartum: 88.07 ± 35.63 pg/mL; pregnancy: 75.24 ± 37.90 pg/mL, p = 0.004). SCGN was directly correlated with week of gestation (rp = 0.308; p = 0.021) and triglycerides (rp = 0.276; p = 0.038) in women with GDM. Therefore, SCGN is related to insulin secretion and hyperinsulinemia during pregnancy; however, it does not display differences between women with NGT and GDM.

show abstract

Secretagogin in the brain and pituitary of the catfish, Clarias batrachus: Molecular characterization and regulation by insulin

Basu

Mitra

Singh

et al. 2022

J of Comparative Neurology

View full text Add to dashboard Cite

Secretagogin (scgn), is a novel hexa EF-hand, phylogenetically conserved calciumbinding protein. It serves as Ca 2+ sensor and participates in Ca 2+ -signaling and neuroendocrine regulation in mammals. However, its relevance in the brain of nonmammalian vertebrates has largely remained unexplored. To address this issue, we studied the cDNA encoding scgn, scgn mRNA expression, and distribution of scgnequipped elements in the brain and pituitary of a teleost, Clarias batrachus (cb). The cbscgn cDNA consists of three transcripts (T) variants: T1 (2185 bp), T2 (2151 bp) and T3 (2060 bp). While 816 bp ORF in T1 and T2 encodes highly conserved six EF-hand 272 aa protein fully capable of Ca 2+ -binding, 726-bp ORF in T3 encodes 242 aa protein.The T1 showed >90% and >70% identity with scgn of catfishes, and other teleosts and mammals, respectively. The T1-mRNA was widely expressed in the brain and pituitary, while the expression of T3 was restricted to the telencephalon. Application of the antiscgn antiserum revealed a ∼32 kDa scgn-immunoreactive (scgn-i) band (known molecular weight of scgn) in the forebrain tissue, and immunohistochemically labeled neurons in the olfactory epithelium and bulb, telencephalon, preoptic area, hypothalamus, thalamus, and hindbrain. In the pituitary, scgn-i cells were seen in the pars distalis and intermedia. Insulin is reported to regulate scgn mRNA in the mammalian hippocampus, and feeding-related neuropeptides in the telencephalon of teleost. Intracranial injection of insulin significantly increased T1-mRNA expression and scgn-immunoreactivity

show abstract

Secretagogin Regulates Insulin Signaling by Direct Insulin Binding

Cited by 24 publications

References 66 publications

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

Secretagogin is Related to Insulin Secretion but Unrelated to Gestational Diabetes Mellitus Status in Pregnancy

Secretagogin in the brain and pituitary of the catfish, Clarias batrachus: Molecular characterization and regulation by insulin

Contact Info

Product

Resources

About