The earliest detectable defect in -cell function is commonly thought to be a reduction in first-phase insuli Continue reading >> An immediate first phase of insulin secretion occurs over 3 minutes and is followed by a more prolonged second phase of insulin secretion. This study aimed to evaluate the 2 phases of ISEC in newly diagnosed type 2 diabetes mellitus patients. Therefore, although the importance of 2nd phase insulin secretion is relatively underestimated compared to that in the 1st phase, it is important for maintaining glucose homeostasis. Phasic insulin secretion measured by in situ pancreatic perfusion after treatment with 0.1 mM MBCD shows a blunted first phase secretion as well as an attenuated second phase (Fig. Diabetes (type II) is associated with abnormalities in this release pattern. In health, a rise in blood glucose triggers a biphasic pattern of insulin response, consisting of a rapid (<10 min) first phase and a less prominent but sustained second phase. SPIR index is defined as the area under the curve of insulin between 8 and 90 min after an Intravenous Glucose Tolerance Test (IVGTT). Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information. There are 2 phases of ISEC: the first phase (first ISEC) and second phase (second ISEC). 2). Ca+2 channels. First phase insulin secretion occurs very rapidly, usually within 10 minutes of glucose stimulation. Second phase insulin secretion is more gradual and long lasting, occurring 25 30 minutes after glucose stimulation. The glycolysis pathway. The second phase of insulin secretion follows the first phase and continues till the normal glucose levels achieved. Abstract Aim: Impaired insulin sensitivity and insulin secretion (ISEC) are major pathophysiologies of type 2 diabetes (T2DM). 2, AC and Table 2).Treatment with exenatide increased plasma insulin (P < 0.005) and C-peptide integrated incremental responses (P < 0.005) during the first (010 min) and second (10120 min) phases of glucose-stimulated First-phase insulin secretion: In response to i.v. Their effects on insulin secretion, cellular calcium metabolism, protein phosphorylation, This observation led to the concept proposed by Grodsky of distinct subcellular pools of insulin. An immediate first phase of insulin secretion occurs over 3 minutes and is followed by a more prolonged second phase of insulin secretion. Second-Phase Insulin Injection. This reaction could, for example, contribute to late postprandial glucose regulation by suppressing hepatic glucose production by portal venous insulin. There are two phases of the insulin secretion, the first phase involves the L-type Ca+2 channels and the second phase involves the R-type Ca+2 channels. Researchers have identified two distinct phases of insulin secretion by the pancreas that occur when study subjects are given an intravenous glucose injection. First, they reported that first-phase and second-phase insulin secretion is even enhanced in a GLP-1 concentration-dependent manner under 16.7 mmol/L glucose in rat islets. This observation led to the concept proposed by Grodsky of distinct subcellular pools of insulin. The insulin peak in the first secretion phase appeared 35 min after intravenous injection of glucose and remained for approximately 10 min. More important, it increases glucose utilization in peripheral tissues . control insulin secretion. A second phase of insulin secretion begins at around 10 minutes and is maintained until circulating glucose levels return to normal. Second phase secretion will be induced by either the phorbol ester, TPA, or the diglycerides 1-acetyl, 2-arachidonyl glycerol and 1-oley1 2-acetyl glycerol. 5,75,76 More recently, these hypothetical pools have developed a likely anatomic basis. it is a biphasic response, in which the first release begins within a few minutes of stimulation, after which it declines. ISEC has two phases: the first and second phases (second ISEC). There are two phases of the insulin secretion, the first phase involves the L-type Ca+2 channels and the second phase involves the R-type Ca+2 channels. Arslanian, S., Austin, A. DETERMINANTS OF FIRST & SECOND PHASE INSULIN SECRETION (FPIS, SPIS) IN HEALTHY ADOLESCENTS. Insulin secretion mechanism is a common example of signal transduction pathway mechanism. Insulin secretion. The 2nd phase insulin secretion of GSIS reduces HGP as in 1st phase, but to a lesser extent . The temporal and spatial control of Cdc42 and Rac1 activity, as well as its corresponding GDIs and GEFs, play important roles in regulating the second phase of insulin release. Glucose-stimulated insulin secretion consists of a transient first phase followed by a sustained second phase. 10.1210/jc.2017-01342. Medicine. There are 2 phases of ISEC: the first phase (first ISEC) and second phase (second ISEC). Increased early phase insulin secretion and RRP size in GRK2+/ mice. the first- and second phase insulin secretion (FPIS, SPIS, respectively) [6, 7]. Totally, 82 subjects, including 15 with normal fasting glucose, 26 with pre-diabetes and 41 with T2DM A similar preferential effect on late-phase insulin secretion is observed in CaV2.3/ mice (Figure 4 ). Study Design. Monday , May 9 2022 [106]. Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2018, 103, pp.1310 - 1319. Thompson et al. Importantly, Rac1 activation and function was linked in a common pathway downstream of Cdc42; Cdc42 depletion ablated glucose-in-duced Rac1 activation, and expression of constitutively active Rac1 in Cdc42-depleted cells functionally restored glucose-stimulated insulin secretion. This was due to the fact that the 1st phase insulin secretion decreased rapidly early in the stage of prediabetes. Figure 1 shows first-phase insulin secretion (insulin peak at 1 min) for glucose alone and for GIP and GLP-1 in combination with glucose at 0.003, 0.03, 0.3, and 3.0 nmol/kg. The effects of glibenclamide on ionic mechanisms and mobility of insulin granules were also studied. N2 - Impaired insulin secretion (ISEC) has been recognized as one of the most important pathophysiologies of type 2 diabetes mellitus. First phase insulin secretion occurs very rapidly, usually within 10 minutes of glucose stimulation. Glucose-stimulated insulin secretion consists of a transient first phase followed by a sustained second phase. Diabetes (type II) is associated with abnormalities in this release pattern. Thus, glucose-insulin homeostasis maintained which helps to maintain the steady metabolism of the body. As a result, glucose amplification of KCl-induced insulin secretion remained unchanged (2.0- vs. 1.7-fold for first phase and 1.8- vs. 2.0-fold for second phase; Fig. In this study, we derived equations to identify patients with second ISEC deficiency (ISEC-D). The 1st phase insulin secretion was a very sensitive indicator which reflected the change of fasting plasma glucose level [26, 27]. 2. 2020;99:12(e19562). Ca+2 channels. of biphasic insulin secretion. The first phase involves a sharp increase in insulin secretion within 5 min, followed by a second phase, during which moderate insulin secretion lasts for hours (9, 12). Pediatr Res 33, S74 (1993). The second phase of insulin secretion is directly related to the level of glucose elevation . Phase 2.As OGTT-based indices of insulin secretion and insulin sensitivity share many of the same measurements of glucose and insulin (i.e., fasting values, 120-min values), the possibility of statistical auto-correlation as a basis for any apparent hyperbolic relationship must be considered ((), ()).For this reason, combinations identified in phase 1 were next evaluated using Here we demonstrate that pharmacological inhibition of R-type Ca V 2.3 Ca 2+ channels using SNX482 does not affect first-phase insulin secretion, but reduces second-phase release a dramatic 80%. P = 0.042 for first phase, P = AbstractIt has been established that prediabetes can causes significant comorbidities, particularly in the elderly. It is the prolonged phase of insulin secretion. The first and second phase of insulin secretion in naive Chinese type 2 diabetes mellitus. Pancreatic -cell insulin secretion plays a central role in maintaining glucose homeostasis. Insulin secretion is biphasic in response to either glucose or amino acid stimuli. Abstract: The purpose of the present study was to test the efficacy of the empiric index SPIR (Second-phase Insulin Release) in the quantification of second-phase insulin secretion in the Zucker Fatty Rat. These findings reveal TALK-1 channels as important modulators of second-phase insulin secretion and suggest a clinically relevant mechanism for rs1535500, which may increase type 2 diabetes risk by limiting GSIS. Impaired insulin secretion (ISEC) has been recognized as one of the most important pathophysiologies of type 2 diabetes mellitus. to maintain glucose homeostasis. Lin JD, Hsia TL, Wu CZ, Su CC, Ma WY, Hsieh AT, Hsieh CH, Wang K, Chu YM, Pei D. Metabolism, 59(6):780-786, 16 Dec 2009 Cited by: 12 articles | PMID: 20005535 few studies have focused on the role of insulin secre-tion compared to insulin resistance. Effects of Exenatide on First and Second Phase Insulin Secretion in Response to Intravenous Glucose in Subjects with Type 2 Diabetes Exenatide (synthetic exendin-4 Exenatide (synthetic exendin-4) increases insulin secretion (IS) during hyperglycemia. Exenatide Augments First- and Second-Phase Insulin Secretion in Response to Intravenous Glucose in Subjects with Type 2 Diabetes The Journal of Clinical Endocrinology & Metabolism, 2005 Michael Trautmann Glucose caused a much more pronounced first phase release than did a complete amino acid mixture; whereas glucose and the amino acid mixture stimulated late second phase insulin secretion equipotently. These changes are similarly found in isolated Cx36 -/-islets. Here we review the evidence that biphasic insulin secretion reflects exocytosis of two functional subsets of secretory granules and the implications for diabetes. KCl has been used to induce the first phase of insulin secretion by membrane depolarization followed by increased intracellular Ca 2+, whereas glucose is used to evoke both first- and second-phase insulin release through the K ATP channel-independent amplification pathway [3133]. As Cdc42 functions only to regulate second-phase secretion, the authors speculate that the impaired glucose-stimulated insulin secretion observed is specifically in the second phase. TSGH-C108-142. Thus, if these late insulin responses reflect second-phase insulin release, this phase of insulin secretion may also have been reduced. 2D). Some studies have shown that first phase insulin secretion (1st ISEC) nearly disappears even before type 2 diabetes is diag-nosed [5-8], although second phase insulin secretion (2nd ISEC) remains partially functional after the diagno-sis [9]. Hence, the insulin content in the medium of isolated islet is consisting of insulin secretion and amount or formation of insulin [20, 21]. Glucose-stimulated insulin secretion has a biphasic pattern, which consists of a 10- to 15-min rapid first phase and a less-prominent but sustained second phase . Luzi L, DeFronzo RA. The initial spike response is generally referred to as first-phase insulin release, and the subsequent increase in insulin secretion is considered to represent the second-phase insulin release. In patients with T2DM, one of the earliest manifestations of defective -cell function is the loss of the first phase and a decrease in the second phase of 2. The second phase of ISec was estimated by BCS, described by Mari and calculated as the slope (pmol/min/m 2) of the relationship between ISR and glucose concentration, and by the S index, described by Breda, including the insulin second-phase response to the meal test challenge. In this study, we derived equations to identify patients with second ISEC deficiency (ISEC-D). However, Cx36 -/-mice exhibit reduced insulin pulse amplitudes and a reduction in first-phase insulin secretion. A loss of the GSIS first phase is closely associated with the future development of T2D ( 9 , 13 , 14 ). The deterioration of glucose metabolism are generally considered to be results of the impairment of the 4 factors: first, second insulin secretion (FPIS, SPIS, respectively), glucose effectiveness (GE), and insulin resistance. n = 4. Previous studies showed that the FPIS is lost in the early stage of T2DM but the SPIS is only blunted [8, 9]. The incretin mimetic exenatide has glucoregulatory activities in DM2, including glucose-dependent enhancement of insulin secretion. ABSTRACT Objective We denote the four major factors related to the development of type 2 diabetes (T2D) as diabetes factor (DF); increased insulin resistance (IR); decreased glucose effectiveness (GE); and the first-and-second-phase of insulin secretion (FPIS, SPIS). First phase insulin secretion occurs very rapidly, usually within 10 minutes of glucose stimulation. The concept that the first phase reflects release of preformed insulin and that the second phase reflects release of newly synthesized insulin is also not correct . There are two phases of insulin secretion, i.e. CiteSeerX - Document Details (Isaac Councill, Lee Giles, Pradeep Teregowda): Context: First-phase insulin secretion (within 10 min after a sudden rise in plasma glucose) is reduced in type 2 diabetes mellitus (DM2). Islet perifusion experiments are required to provide a more definitive answer into the role of PIX on the second phase of insulin release. Figure 4. The underlying mechanism that leads to the more sustained nature of the second phase is under active investigation. The second phase of prandial insulin secretion follows, and is sustained until normoglycemia is restored. One disconnect in the importance of Rac1 in supporting second-phase insulin release is that Rac1 activation does not occur until the second phase of secretion is well under way. The second signaling cascade is also called the (K ATP)-independent pathway. This contains newly formed insulin released immediately. In this study we demonstrate that RhoGDI is a key regulator of the second phase of insulin secretion from pancreatic islets, functioning as a master coordinator of the differential temporal activation events of the two critical GTPases involved in the process, Cdc42 and Rac1. In this study, we tried to build an equation to predict 2nd ISEC. Insulin secretion mechanism is a common example of signal transduction pathway mechanism. Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans. Pancreatic -cells secrete insulin in a biphasic manner, first and second phase production and priming insulin sensitive tissue to more readily take up glucose and has thus prompted numerous among others, hypoxia inducible factor 1, von Hippel-Lindau, factor as distal regulators of second-phase secretion. 1982;31:964-972. Primary islets from Tcad-KO mice were defective in glucose-induced but not KCl-mediated insulin secretion. fusion of insulin-containing vesicles with the plasma membrane [18] representing the first phase of insulin secretion. First and second phase insulin secretion were found to be highest in LP, compared with both EPP and LPP (p<0.001). Figure 2 shows first and second phase insulin secretion and C-peptide and plasma glucose concentrations at every visit. We conclude that both phases of insulin release are vital to full counterregulation of the action of glucagon on glucose metabolism. oGTT (2 g/kg) was performed in Introduction. As mentioned before, one possible role for Rac1 may be in F-actin formation and granule corralling as part of the metering mechanism of granule pool refilling. 3 C ) but slightly increased tolbutamide-induced insulin secretion in low glucose. ISEC has two phases: the first and second phases (second ISEC). First-phase and second-phase insulin secretion rates and total insulin secretion rate indices were obtained as areas under the curve (AUC) of insulin secretion rate at selected time intervals. Abstract:Type 2 diabetes (T2D) is a metabolic disorder characterised by the inability of -cells to secrete enough insulin to maintain glucose homeostasis. First-phase insulin release is important to counter the quick effect of glucagon on glucose production, while second-phase insulin release is important to sustain that inhibition and to augment glucose utilization. It is characterized by a lower amplitude and longer duration and lasts as long as the secretory stimulus is active on the beta cells. The second phase of insulin secretion is separated from the first phase by a nadir. (1995) used the AIR as a measure of insulin secretory function in linkage analyses in Pima Indians and localized a genetic element on chromosome 1p31 near the short tandem repeat marker (STRP) D1S198. The results indicate glibenclamide binding at receptors internalized within the beta cell that functionally contribute to sustained second phase insulin secretion, apart from the plasma membrane K-ATP channels sites. Insulin is produced by the pancreas in a region called Islets of Langerhans. The underlying mechanism that leads to the more sustained nature of the second phase is under active investigation. First-phase insulin secretion is triggeredbytherisein[Ca2+] c that occurs synchronously in all beta cells of every islet in response to a sudden increase in the glucose concentration. It is characterized by a lower amplitude and longer duration and lasts as long as the secretory stimulus is active on the beta cells. Two phases of insulin secretion are widely known: the first-phase insulin secretion (FPIS) and the second-phase insulin secretion (SPIS). 3. Diabetes. The first/early phase of insulin secretion is critical in maintaining the PPG homeostasis, and can prevent chronic postprandial hyperglycemia [51] [52] [53]. The second phase of insulin secretion is gradual and is dependent on the degree and duration of glucose stimulation [51, 52]. Pancreatic -cells secrete insulin in a biphasic manner, first and second phase insulin secretion, and loss of first phase insulin secretion is an independent predictor of T2D onset. The relative importance of first- and second-phase insulin secretion in countering the action of glucagon on glucose turnover in the conscious dog.