scholarly journals Pancreatic Thyrotropin Releasing Hormone and Mechanism of Insulin Secretion

2018 ◽  
Vol 50 (1) ◽  
pp. 378-384 ◽  
Author(s):  
Vladimír  Štrbák
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Basal Insulin ◽  
Thyrotropin Releasing Hormone ◽  
Insulin Content ◽  
Β Cells ◽  
Releasing Hormone ◽  
Rat Pancreatic Islets ◽  
Basal Insulin Secretion

Thyrotropin releasing hormone (TRH; pGlu-His-ProNH2) is expressed also in pancreatic β cells where it is colocalized in secretory granules with insulin. High perinatal changes of the TRH gene expression and TRH concentrations in rat pancreatic islets coincide with the perinatal maturation of the adequate insulin secretory responsiveness to glucose and other nutrient secretagogues. TRH secretion from pancreatic islets is stimulated by glucose and inhibited by insulin. Disruption of the TRH gene in knockout mice results in hyperglycemia accompanied by impaired insulin secretory response to glucose. Progress in understanding TRH - insulin relations may be substantial for improving knowledge of pathophysiological mechanisms included in changes of insulin secretion with possible clinical impact. Block of the last step of biosynthesis of α-amidated peptides, including TRH by disulfiram (DS) treatment of adult male rats subcutaneously with 200 mg/kg for five days in our experiments resulted in barely detectable levels of peptidyl-glycine α-amidating monooxygenase (PAM) in their pancreatic islets. TRH in physiological concentration (1 nM) does not affect basal insulin secretion from intact rat pancreatic islets. In contrast, basal insulin secretion from islets of DS-treated rats is four times higher compared to controls and could not be further stimulated by high-glucose. The addition of 1 nM TRH into medium decreased immediately basal insulin secretion in DS (TRH lacking) islets to control level and normalized also their response to glucose. Interestingly, absence of the secretory response to glucose in islets from TRH depleted rats was connected with their increase of insulin content during stimulation. Glucose stimulation together with 1 nM TRH normalized also insulin content in DS islets. Apparently, high insulin content in islets from TRH depleted animals is a result of block of regulatory secretion pathway redirected to constitutional secretion which was corrected by the addition of TRH. Type 2 diabetes mellitus is a disease characterized by various range from predominant insulin resistance with relative insulin deficiency to a predominant secretory defect with insulin resistance. These symptoms suggest a possible role of TRH dysregulation. In conclusion, presence of TRH in β cells ensures appropriate low basal (constitutive) insulin secretion. Release of TRH induced by glucose and possibly by other secretagogues has autocrine effect resulting in directing insulin secretion to regulatory pathway reacting to stimulation. If some defects of insulin secretion could be treated by TRH, various ways of applications (also oral and nasal) could be utilized. Moreover, positive side effects shown in animal experiments may accompany the treatment: TRH has the potential to prevent apoptosis and promotes insulin-producing cell proliferation and has also aging-reversing properties.

Relationship between insulin secretion, insulin content and dry weight of single rat pancreatic islets

1980 ◽  
Vol 94 (3) ◽  
pp. 365-370
Author(s):  
G. H. J. Wolters ◽  
W. Konijnendijk
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Outer Surface ◽  
Basal Insulin ◽  
Dry Weight ◽  
Insulin Content ◽  
Curvilinear Relationship ◽  
Rat Pancreatic Islets ◽  
Basal Insulin Secretion

Abstract. Single islets were incubated at glucose 5 mm for 60 min and subsequently at glucose 15 mm for 30 min. The insulin content of the incubated islets was proportional to the dry weight of the islets. The insulin secretion (Y) demonstrated a curvilinear relationship with the dry weight (X) of the islets, which could be described by the function Y = aX⅔ (a being a constant). On basis of this function it can be calculated that the insulin secretion of a particular islet is proportional to its outer surface. The consequence of this is that small sized islets secrete relatively much more insulin than large islets. Islets isolated with either purified or crude collagenase gave the same results except that a higher basal insulin secretion was observed with crude collagenase.

Leptin suppresses basal insulin secretion from rat pancreatic islets

1997 ◽  
Vol 70 (2-3) ◽  
pp. 179-182 ◽  
Author(s):  
Kaori Ishida ◽  
Takashi Murakami ◽  
Akira Mizuno ◽  
Mitsuru Iida ◽  
Masamichi Kuwajima ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Basal Insulin ◽  
Rat Pancreatic Islets ◽  
Basal Insulin Secretion

A role of thyrotropin-releasing hormone in insulin secretion by isolated rat pancreatic islets

2004 ◽  
Vol 449 (6) ◽  
pp. 547-552 ◽  
Author(s):  
Miroslava Najvirtová ◽  
Zuzana Bačová ◽  
Adela Mátéffyová ◽  
Vladimír Štrbák
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Thyrotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Rat Pancreatic Islets ◽  
Isolated Rat

scholarly journals Sweet Taste Receptors Regulate Basal Insulin Secretion and Contribute to Compensatory Insulin Hypersecretion During the Development of Diabetes in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2112-2121 ◽  
Author(s):  
George A. Kyriazis ◽  
Kathleen R. Smith ◽  
Björn Tyrberg ◽  
Tania Hussain ◽  
Richard E. Pratley
Keyword(s):  
Insulin Secretion ◽  
Mouse Models ◽  
Basal Insulin ◽  
Sweet Taste ◽  
Human Islets ◽  
Continuous Exposure ◽  
Taste Receptors ◽  
Β Cells ◽  
Sweet Taste Receptors ◽  
Basal Insulin Secretion

β-Cells rapidly secrete insulin in response to acute increases in plasma glucose but, upon further continuous exposure to glucose, insulin secretion progressively decreases. Although the mechanisms are unclear, this mode of regulation suggests the presence of a time-dependent glucosensory system that temporarily attenuates insulin secretion. Interestingly, early-stage β-cell dysfunction is often characterized by basal (ie, fasting) insulin hypersecretion, suggesting a disruption of these related mechanisms. Because sweet taste receptors (STRs) on β-cells are implicated in the regulation of insulin secretion and glucose is a bona fide STR ligand, we tested whether STRs mediate this sensory mechanism and participate in the regulation of basal insulin secretion. We used mice lacking STR signaling (T1R2−/− knockout) and pharmacologic inhibition of STRs in human islets. Mouse and human islets deprived of STR signaling hypersecrete insulin at short-term fasting glucose concentrations. Accordingly, 5-hour fasted T1R2−/− mice have increased plasma insulin and lower glucose. Exposure of isolated wild-type islets to elevated glucose levels reduced STR expression, whereas islets from diabetic (db/db) or diet-induced obese mouse models show similar down-regulation. This transcriptional reprogramming in response to hyperglycemia correlates with reduced STR function in these mouse models, leading to insulin hypersecretion. These findings reveal a novel mechanism by which insulin secretion is physiologically regulated by STRs and also suggest that, during the development of diabetes, STR function is compromised by hyperglycemia leading to hyperinsulinemia. These observations further suggest that STRs might be a promising therapeutic target to prevent and treat type 2 diabetes.

Four-week ethanol drinking increases both thyrotropin-releasing hormone (TRH) release and content in rat pancreatic islets

Life Sciences ◽  
2000 ◽  
Vol 66 (7) ◽  
pp. 629-639 ◽  
Author(s):  
J. Benický ◽  
M. Nikodémová ◽  
S. Scsuková ◽  
Š. Zórad ◽  
V. Štrbák
Keyword(s):  
Pancreatic Islets ◽  
Thyrotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Rat Pancreatic Islets ◽  
Ethanol Drinking

scholarly journals Direct Stimulation of Basal Insulin Secretion by Physiological Concentrations of Leptin in Pancreatic β Cells

Endocrinology ◽  
1997 ◽  
Vol 138 (10) ◽  
pp. 4513-4516 ◽  
Author(s):  
Yukio Tanizawa ◽  
Shigeru Okuya ◽  
Hisamitsu Ishihara ◽  
Tomoichiro Asano ◽  
Toshihiko Yada ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Basal Insulin ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Direct Stimulation ◽  
Basal Insulin Secretion ◽  
Stimulation Of

scholarly journals Insulin Secretion Is Increased in Pancreatic Islets of Neuropeptide Y-Deficient Mice

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5716-5723 ◽  
Author(s):  
Yumi Imai ◽  
Hiral R. Patel ◽  
Evan J. Hawkins ◽  
Nicolai M. Doliba ◽  
Franz M. Matschinsky ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Neuropeptide Y ◽  
Pancreatic Islets ◽  
High Fat Diet ◽  
Basal Insulin ◽  
High Fat ◽  
Y1 Receptor ◽  
Basal Insulin Secretion ◽  
Glucose Stimulated Insulin Secretion ◽  
Deficient Mice

Neuropeptide Y (NPY), whose role in appetite regulation is well known, is also expressed in pancreatic islets. Although previous studies indicated that application of NPY to pancreatic islets inhibits insulin secretion, its physiological role in the regulation of insulin secretion is not fully understood. We hypothesized that NPY in islets tonically suppresses insulin secretion and the reduction of islet NPY increases insulin secretion. To address the hypothesis, islet function of NPY-deficient mice was analyzed. Although there was little change in glucose homeostasis in vivo, pancreatic islets from NPY-deficient mice had higher basal insulin secretion (1.5 times), glucose-stimulated insulin secretion (1.5 times), and islet mass (1.7 times), compared with wild-type mouse. Next we sought to determine whether the expression of NPY and Y1 receptor in islets was altered in hyperinsulinemia associated with obesity. Islets from C57BL/6J mice on a high-fat diet had 1.9 times higher basal insulin secretion and 2.4 times higher glucose-stimulated insulin secretion than control mice, indicating islet adaptation to obesity. Expression of NPY and Y1 receptor mRNA levels was decreased by 70 and 64%, respectively, in high-fat diet islets, compared with controls. NPY and Y1 receptor in islets were also reduced by 91 and 80%, respectively, in leptin-deficient ob/ob mice that showed marked hyperinsulinemia. Together these results suggest that endogenous NPY tonically inhibits insulin secretion from islets and a reduction of islet NPY may serve as one of the mechanisms to increase insulin secretion when islets compensate for insulin resistance associated with obesity.

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