Insulin secretion by rat lachrymal glands: effects of systemic and local variables

2005 ◽  
Vol 289 (5) ◽  
pp. E768-E775 ◽  
Author(s):  
Daniel Andrade Cunha ◽  
Everardo M. Carneiro ◽  
Mônica de C. Alves ◽  
Angélica Gobbi Jorge ◽  
Sylvia Morais de Sousa ◽  
...  

To understand the secretory mechanisms and physiological role of insulin in the tear film, the present study examined 1) the time course of insulin secretion in the tear film under glucose intravenous stimulation, 2) the glucose- and carbachol-induced insulin secretion from isolated lachrymal gland (LG), 3) the effect of insulin on glucose consumption by the cornea, and 4) the expression of insulin, pancreatic duodenal homeobox-1 (PDX-1), and glucose transport proteins (GLUTs) in LG tissue. The insulin level in the tear film of 8-wk-old male Wistar rats increased from 0.6 ± 0.45 to 3.7 ± 1.3 ng/ml in the initial minutes after glucose stimulation. In vitro assays demonstrated that higher glucose concentrations from 2.8 to 16.7 mM, 200 μM carbachol, or 40 mM KCl significantly increased insulin secretion from lacrimal glands compared with controls, but did not detect C-peptide as measured by RIA. Glucose consumption by corneal tissue, evaluated by radiolabeled d-[U-14C]glucose uptake, was 24.07 ± 0.61 and was enhanced to 31.63 ± 3.15 nmol·cornea−1·2 h−1 in the presence of 6 nM insulin ( P = 0.033) and to 37.5 ± 3.7 nmol·cornea−1·2 h−1 in the presence of 11.2 mM glucose ( P = 0.015). Insulin and PDX-1 mRNA was detected in LG. Insulin was located in the apical areas of acinar cells by immunoperoxidase and the expression of GLUT-1, but not PDX-1, was confirmed by Western blot. These findings suggest that insulin secretion in the tear film is influenced by local stimuli such as nutrient and neural inputs and that this hormone plays a metabolic role in ocular surface tissues. These data also indicate that under normal conditions the insulin secreted by LG is stored, but it is not clear that is locally produced in the LG.

2003 ◽  
Vol 14 (9) ◽  
pp. 3592-3604 ◽  
Author(s):  
Dirk Wienke ◽  
John R. MacFadyen ◽  
Clare M. Isacke

Endo180, a member of the mannose receptor family, is constitutively recycled between clathrin-coated pits on the cell surface and intracellular endosomes. Its large extracellular domain contains an N-terminal cysteine-rich domain, a single fibronectin type II domain and eight C-type lectin-like domains. The second of these lectin-like domains has been shown to mediate Ca2+-dependent mannose binding. In addition, cross-linking studies have identified Endo180 as a urokinase plasminogen activator receptor–associated protein and this interaction can be blocked by collagen V. Here we demonstrate directly using in vitro assays, cell-based studies and tissue immunohistochemistry that Endo180 binds both to native and denatured collagens and provide evidence that this is mediated by the fibronectin type II domain. In cell culture systems, expression of Endo180 results in the rapid uptake of soluble collagens for delivery to lysosomal degradative compartments. Together with the observed restricted expression of Endo180 in both embryonic and adult tissue, we propose that Endo180 plays a physiological role in mediating collagen matrix remodelling during tissue development and homeostasis and that the observed receptor upregulation in pathological conditions may contribute to disease progression.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alonso Zavafer ◽  
Ievgeniia Iermak ◽  
Mun Hon Cheah ◽  
Wah Soon Chow

AbstractThe quenching of chlorophyll fluorescence caused by photodamage of Photosystem II (qI) is a well recognized phenomenon, where the nature and physiological role of which are still debatable. Paradoxically, photodamage to the reaction centre of Photosystem II is supposed to be alleviated by excitation quenching mechanisms which manifest as fluorescence quenchers. Here we investigated the time course of PSII photodamage in vivo and in vitro and that of picosecond time-resolved chlorophyll fluorescence (quencher formation). Two long-lived fluorescence quenching processes during photodamage were observed and were formed at different speeds. The slow-developing quenching process exhibited a time course similar to that of the accumulation of photodamaged PSII, while the fast-developing process took place faster than the light-induced PSII damage. We attribute the slow process to the accumulation of photodamaged PSII and the fast process to an independent quenching mechanism that precedes PSII photodamage and that alleviates the inactivation of the PSII reaction centre.


Reproduction ◽  
2014 ◽  
Vol 148 (3) ◽  
pp. 259-270 ◽  
Author(s):  
Georgios Michailidis ◽  
Maria Anastasiadou ◽  
Edith Guibert ◽  
Pascal Froment

Sertoli cells (SCs) play an important physiological role in the testis, as they support, nourish, and protect the germ cells. As protection of the developing spermatozoa is an emerging aspect of reproductive physiology, this study examined the expression pattern of innate immune-related genes, including avian β-defensins (AvBDs), Toll-like receptors (TLRs), and cytokines, and investigated the time course of an inflammatory response in rooster SCs triggered by exposure to the bacterial endotoxin lipopolysaccharide (LPS). SCs were isolated from 6-week-old chicken, culturedin vitro, and stimulated with 1 μg/ml LPS at different time courses (0, 6, 12, 24, and 48 h). Data on expression analysis revealed that all ten members of the chickenTLRfamily, nine members of theAvBDfamily, as well as eight cytokine genes were expressed in SCs. Quantitative real-time PCR analysis revealed that LPS treatment resulted in significant induction of the expression levels of sixTLRs, sixAvBDs, and four cytokine genes, while two cytokine genes were downregulated and two other genes were unchanged. The increasing interleukin 1β (IL1β) production was confirmed in the conditioned medium. Furthermore, the phagocytosis of SCs was increased after LPS treatment. In conclusion, these findings provide evidence that SCs express innate immune-related genes and respond directly to bacterial ligands. These genes represent an important component of the immune system, which could be integrated into semen, and present a distinctive constituent of the protective repertoire of the testis against ascending infections.


2013 ◽  
Vol 66 (5-6) ◽  
pp. 259-262
Author(s):  
Goran Marusic ◽  
Dimitrije Jeremic ◽  
Sasa Vojinov ◽  
Natasa Filipovic ◽  
Milan Popov

In addition to the metabolic role of vitamin D, which is well known and clearly defined, there have been many hypotheses regarding its anti-proliferative and pro-apoptotic role. Epidemiology and Significance of Prostate Cancer. Prostate cancer is the second most common malignancy in men. Long period of cancerogenesis, available tumor markers and high incidence make this cancer ideal for preventive measures. Physiological Role of Vitamin D and its Effect on Prostate Cancer Cells. In vitro and in vivo studies have shown the anti-proliferative and pro-apoptopic role of vitamin D. Disorders of vitamin D metabolism are noted in vitamin D gene level, vitamin D receptor, vitamin D responsive elements and androgen receptors. We present the most important effect of those changes on vitamin D metabolism. Conclusion. Available studies on vitamin D level in serum, prostate tissue, observed activity of vitamin D enzymes and genetic changes give us only a slight insight into the basic mechanisms of vitamin D action in the development of prostate cancer; therefore, further investigations are needed.


2012 ◽  
Vol 302 (4) ◽  
pp. E403-E408 ◽  
Author(s):  
Mika Bando ◽  
Hiroshi Iwakura ◽  
Hiroyuki Ariyasu ◽  
Hiroshi Hosoda ◽  
Go Yamada ◽  
...  

Whereas ghrelin is produced primarily in the stomach, a small amount of it is produced in pancreatic islets. Although exogenous administration of ghrelin suppresses insulin secretion in vitro or in vivo, the role of intraislet ghrelin in the regulation of insulin secretion in vivo remains unclear. To understand the physiological role of intraislet ghrelin in insulin secretion and glucose metabolism, we developed a transgenic (Tg) mouse model, rat insulin II promoter ghrelin-internal ribosomal entry site-ghrelin O-acyl transferase (RIP-GG) Tg mice, in which mouse ghrelin cDNA and ghrelin O-acyltransferase are overexpressed under the control of the rat insulin II promoter. Although pancreatic desacyl ghrelin levels were elevated in RIP-GG Tg mice, pancreatic ghrelin levels were not altered in animals on a standard diet. However, when Tg mice were fed a medium-chain triglyceride-rich diet (MCTD), pancreatic ghrelin levels were elevated to ∼16 times that seen in control animals. It seems likely that the gastric ghrelin cells possess specific machinery to provide the octanoyl acid necessary for ghrelin acylation but that this machinery is absent from pancreatic β-cells. Despite the overexpression of ghrelin, plasma ghrelin levels in the portal veins of RIP-GG Tg mice were unchanged from control levels. Glucose tolerance, insulin secretion, and islet architecture in RIP-GG Tg mice were not significantly different even when the mice were fed a MCTD. These results indicate that intraislet ghrelin does not play a major role in the regulation of insulin secretion in vivo.


2005 ◽  
Vol 187 (1) ◽  
pp. 159-166 ◽  
Author(s):  
M Alves ◽  
D Andrade Cunha ◽  
V Cristine Calegari ◽  
M J A Saad ◽  
A Carlos Boschero ◽  
...  

Advanced glycation end products (AGEs) increase with aging and induce signaling alterations that lead to inflammation and dysfunction in several tissues. Aging reduces function and insulin signaling in lacrimal glands (LGs). To evaluate whether AGE signaling and insulin secretion in LGs are altered in aging, 24- and 2-month-old male Wistar rats were compared. Immunohistochemistry with confocal microscopy was used to evaluate AGE, AGE receptor (RAGE) and nuclear factor-κB (NF-κB) expression in LGs. Basal tear secretion volume, insulin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in tears and LGs and peroxidase activity in LG tissue were measured. Insulin secretion from isolated LGs and pancreatic β-cells was compared in the supernatant of aging and control rats in vitro by RIA after stimulation with 2.8–16.7 mM glucose, carbachol and KCl. AGE, RAGE and NF-κB expression was higher in LGs of aging compared with young rats. Basal tear secretion and peroxidase activity were significantly lower in the aging group (P=0.016 for both assays). IL-1β and TNF-α levels were higher in tears of aging rats compared with young rats (P=0.007 and 0.05 respectively); however, even though aging rats were insulin-resistant (as confirmed by the insulin-tolerance test), the insulin levels in the tear film of aging and control rats were similar in vivo and in vitro. The higher expression of AGEs, RAGE and NF-κB in LGs of aging rats is accompanied by systemic insulin resistance and may be involved in LG and tear film alterations but does not affect insulin secretion in the tear film. These observations indicate that metabolic events may be related to LG and tear film dysfunctions in aging.


Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4688-4695 ◽  
Author(s):  
Ye Zhang ◽  
Zhifang Xie ◽  
Guangdi Zhou ◽  
Hai Zhang ◽  
Jian Lu ◽  
...  

Pancreatic β-cells can precisely sense glucose stimulation and accordingly adjust their insulin secretion. Fructose-1,6-bisphosphatase (FBPase) is a gluconeogenic enzyme, but its physiological significance in β-cells is not established. Here we determined its physiological role in regulating glucose sensing and insulin secretion of β-cells. Considerable FBPase mRNA was detected in normal mouse islets and β-cell lines, although their protein levels appeared to be quite low. Down-regulation of FBP1 in MIN6 cells by small interfering RNA could enhance the glucose-stimulated insulin secretion (GSIS), whereas FBP1-overexpressing MIN6 cells exhibited decreased GSIS. Inhibition of FBPase activity in islet β-cells by its specific inhibitor MB05032 led to significant increase of their glucose utilization and cellular ATP to ADP ratios and consequently enhanced GSIS in vitro. Pretreatment of mice with the MB05032 prodrug MB06322 could potentiate GSIS in vivo and improve their glucose tolerance. Therefore, FBPase plays an important role in regulating glucose sensing and insulin secretion of β-cells and serves a promising target for diabetes treatment.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Céline Hivelin ◽  
Sophie Béraud-Dufour ◽  
Christelle Devader ◽  
Amar Abderrahmani ◽  
Sébastien Moreno ◽  
...  

Inhibition of the potassium channels TREK-1 by spadin (SPA) is currently thought to be a promising therapeutic target for the treatment of depression. Since these channels are expressed in pancreatic β-cells, we investigated their role in the control of insulin secretion and glucose homeostasis. In this study, we confirmed the expression of TREK-1 channels in the insulin secreting MIN6-B1 β-cell line and in mouse islets. We found that their blockade by SPA potentiated insulin secretion induced by potassium chloride dependent membrane depolarization. Inhibition of TREK-1 by SPA induced a decrease of the resting membrane potential (ΔVm~12 mV) and increased the cytosolic calcium concentration. In mice, administration of SPA enhanced the plasma insulin level stimulated by glucose, confirming its secretagogue effect observed in vitro. Taken together, this work identifies SPA as a novel potential pharmacological agent able to control insulin secretion and glucose homeostasis.


1980 ◽  
Vol 239 (1) ◽  
pp. E57-E63 ◽  
Author(s):  
W. B. Rhoten

The dynamics of insulin secretion during development of the fetal rat pancreas were investigated. The time of onset of glucose-induced insulin secretion was of special interest. Pancreases from 15- to 22-day-old fetal rats were perifused in vitro with low (0.5 or 0.9 mg/ml) or high (5 mg/ml) concentrations of glucose in the presence or absence of arginine and leucine. Levels of insulin in the perifusate were determined by radioimmunoassay. At day 17, a significant increase in perfusate insulin level was observed in response to arginine and leucine (each at 5 mM), This response was independent of a high concentration of glucose. In addition, perifusate insulin levels were augmented when the concentration of amino acids were kept constant and the glucose concentration was changed from a high level to a low level. On day 20, a monophasic, rapid-onset short-duration rise in insulin release with a high glucose concentration was observed. This response was enhanced by acetylcholine (2.7 x 10(-9) M). At days 21 and 22, insulin levels rose rapidly in the presence of high glucose and remained elevated. The results show that there is considerable precision in the timing of the onset and maturation of the glucose-induced insulin secretory response prenatally and reaffirm that insulin secretion by the fetal beta-cell varies with the stimulus applied.


2010 ◽  
Vol 206 (2) ◽  
pp. 195-204 ◽  
Author(s):  
Yusuke Taguchi ◽  
Yoshie Tasaki ◽  
Kiyoshi Terakado ◽  
Kenichi Kobayashi ◽  
Takeo Machida ◽  
...  

The growth-retarded (grt) mouse shows thyroid dysfunction-related hyporesponsiveness to TSH. Thyroid hormone is a critical regulator of metabolism in many cells; thus, derangement of thyroid function affects many organs and systems. Experiments were conducted focusing on the function of the pancreatic islets in grt mice. We showed occurrence of a fasting hyperglycemia and a decreased plasma insulin level response to a glucose load in grt mice, despite normal insulin molecules being stored in secretory granules of pancreatic islets. We also demonstrated a reduction of insulin secretion in response to glucose administration from islets of grt mice in vitro, while the insulin release in response to KCl stimulation was comparable to that in normal mice, indicating that the isolated islets from grt mice have normal ATP-sensitive K+ channels and postchannel activity. The mRNA expression levels of glucose transporter 2 and glucokinase in the islets of grt mice were similar to those in normal mice. Triiodothyronine administration to grt mice improved insulin secretion very slightly. On the other hand, mRNA for tyrosylprotein sulfotransferase 2 (Tpst2) was found to be expressed in the pancreatic islets of grt mice. Considering that Tpst2 is the responsible gene of grt mice, mutation of which is associated with a poor function of TSH receptor, the findings raise a possibility of involvement of factors including Tpst2 in the insulin hyposecretion in grt mice.


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