Abstract
The detailed characterization and quantification of the kinetics of glucose-stimulated insulin secretion (GSIS) by normal pancreatic islets is of considerable interest for characterizing β-cell dysfunction, assessing the quality of isolated islets, and improving the design of artificial pancreas devices. Here, we performed dynamic evaluation of GSIS by human and mouse islets at high temporal resolution (every minute) in response to different glucose steps using an automated multichannel perifusion instrument. In both species, insulin responses were biphasic (a transient first-phase peak followed by a sustained second-phase), and the amount of insulin released showed a sigmoid-type dependence on glucose concentration. However, compared to murine islets, human islets have (1) a less pronounced first-phase response, (2) a flat secretion rate during second-phase response, (3) a left-shifted concentration response (reaching half-maximal response at 7.9 ± 0.4 vs. 13.7 ± 0.6 mM), and (4) an ~3-fold lower maximal secretion rate (8.3 ± 2.3 vs. 23.9 ± 5.1 pg/min/islet at 30 mM glucose). These results can be used to establish a more informative protocol for the calculation of the stimulation index, which is widely used for islet assessment in both research and clinical applications, but without an accepted standard or clear evidence as to what low- to high-glucose steps can provide better characterization of islet function. Data obtained here suggest that human islet functionality might be best characterized with a dynamic stimulation index obtained with a glucose step from a low of 4–5 to a high of 14–17 mM (e.g., G4 → G16).
| Original language | English (US) |
|---|---|
| Article number | 680 |
| Journal | Frontiers in Endocrinology |
| Volume | 10 |
| DOIs | |
| State | Published - Oct 2 2019 |
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Keywords
- beta cell function
- concentration-response
- glucose-stimulated insulin secretion
- islet assessment
- perifusion
- stimulation index
- type 1 diabetes
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
Cite this
Concentration-Dependency and Time Profile of Insulin Secretion : Dynamic Perifusion Studies With Human and Murine Islets. / Alcazar, Oscar; Buchwald, Peter.
In: Frontiers in Endocrinology, Vol. 10, 680, 02.10.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Concentration-Dependency and Time Profile of Insulin Secretion
T2 - Dynamic Perifusion Studies With Human and Murine Islets
AU - Alcazar, Oscar
AU - Buchwald, Peter
PY - 2019/10/2
Y1 - 2019/10/2
N2 - The detailed characterization and quantification of the kinetics of glucose-stimulated insulin secretion (GSIS) by normal pancreatic islets is of considerable interest for characterizing β-cell dysfunction, assessing the quality of isolated islets, and improving the design of artificial pancreas devices. Here, we performed dynamic evaluation of GSIS by human and mouse islets at high temporal resolution (every minute) in response to different glucose steps using an automated multichannel perifusion instrument. In both species, insulin responses were biphasic (a transient first-phase peak followed by a sustained second-phase), and the amount of insulin released showed a sigmoid-type dependence on glucose concentration. However, compared to murine islets, human islets have (1) a less pronounced first-phase response, (2) a flat secretion rate during second-phase response, (3) a left-shifted concentration response (reaching half-maximal response at 7.9 ± 0.4 vs. 13.7 ± 0.6 mM), and (4) an ~3-fold lower maximal secretion rate (8.3 ± 2.3 vs. 23.9 ± 5.1 pg/min/islet at 30 mM glucose). These results can be used to establish a more informative protocol for the calculation of the stimulation index, which is widely used for islet assessment in both research and clinical applications, but without an accepted standard or clear evidence as to what low- to high-glucose steps can provide better characterization of islet function. Data obtained here suggest that human islet functionality might be best characterized with a dynamic stimulation index obtained with a glucose step from a low of 4–5 to a high of 14–17 mM (e.g., G4 → G16).
AB - The detailed characterization and quantification of the kinetics of glucose-stimulated insulin secretion (GSIS) by normal pancreatic islets is of considerable interest for characterizing β-cell dysfunction, assessing the quality of isolated islets, and improving the design of artificial pancreas devices. Here, we performed dynamic evaluation of GSIS by human and mouse islets at high temporal resolution (every minute) in response to different glucose steps using an automated multichannel perifusion instrument. In both species, insulin responses were biphasic (a transient first-phase peak followed by a sustained second-phase), and the amount of insulin released showed a sigmoid-type dependence on glucose concentration. However, compared to murine islets, human islets have (1) a less pronounced first-phase response, (2) a flat secretion rate during second-phase response, (3) a left-shifted concentration response (reaching half-maximal response at 7.9 ± 0.4 vs. 13.7 ± 0.6 mM), and (4) an ~3-fold lower maximal secretion rate (8.3 ± 2.3 vs. 23.9 ± 5.1 pg/min/islet at 30 mM glucose). These results can be used to establish a more informative protocol for the calculation of the stimulation index, which is widely used for islet assessment in both research and clinical applications, but without an accepted standard or clear evidence as to what low- to high-glucose steps can provide better characterization of islet function. Data obtained here suggest that human islet functionality might be best characterized with a dynamic stimulation index obtained with a glucose step from a low of 4–5 to a high of 14–17 mM (e.g., G4 → G16).
KW - beta cell function
KW - concentration-response
KW - glucose-stimulated insulin secretion
KW - islet assessment
KW - perifusion
KW - stimulation index
KW - type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85073698619&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073698619&partnerID=8YFLogxK
U2 - 10.3389/fendo.2019.00680
DO - 10.3389/fendo.2019.00680
M3 - Article
AN - SCOPUS:85073698619
VL - 10
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
SN - 1664-2392
M1 - 680
ER -