PMID- 38358819
OWN - NLM
STAT- MEDLINE
DCOM- 20240325
LR  - 20240504
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 9
IP  - 6
DP  - 2024 Feb 15
TI  - Molecular mechanism responsible for sex differences in electrical activity of 
      mouse pancreatic beta cells.
LID - 10.1172/jci.insight.171609 [doi]
LID - e171609
AB  - In humans, type 2 diabetes mellitus shows a higher prevalence in men compared 
      with women, a phenotype that has been attributed to a lower peripheral insulin 
      sensitivity in men. Whether sex-specific differences in pancreatic beta cell 
      function also contribute is largely unknown. Here, we characterized the 
      electrophysiological properties of beta cells in intact male and female mouse 
      islets. Elevation of glucose concentration above 5 mM triggered an electrical 
      activity with a similar glucose dependence in beta cells of both sexes. However, 
      female beta cells had a more depolarized membrane potential and increased firing 
      frequency compared with males. The higher membrane depolarization in female beta 
      cells was caused by approximately 50% smaller Kv2.1 K+ currents compared with 
      males but otherwise unchanged KATP, large-conductance and small-conductance 
      Ca2+-activated K+ channels, and background TASK1/TALK1 K+ current densities. In 
      female beta cells, the higher depolarization caused a membrane potential-dependent 
      inactivation of the voltage-gated Ca2+ channels (CaV), resulting in reduced Ca2+ 
      entry. Nevertheless, this reduced Ca2+ influx was offset by a higher action 
      potential firing frequency. Because exocytosis of insulin granules does not show 
      a sex-specific difference, we conclude that the higher electrical activity 
      promotes insulin release in females, improving glucose tolerance.
FAU - Jacobo-Piqueras, Noelia
AU  - Jacobo-Piqueras N
FAU - Theiner, Tamara
AU  - Theiner T
FAU - Geisler, Stefanie M
AU  - Geisler SM
FAU - Tuluc, Petronel
AU  - Tuluc P
LA  - eng
PT  - Journal Article
DEP - 20240215
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - SY7Q814VUP (Calcium)
RN  - 0 (Insulin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Female
MH  - Male
MH  - Humans
MH  - *Insulin-Secreting Cells/metabolism
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Sex Characteristics
MH  - Calcium/metabolism
MH  - Insulin/metabolism
MH  - Glucose/metabolism
PMC - PMC11063940
OTO - NOTNLM
OT  - Cell biology
OT  - Diabetes
OT  - Endocrinology
OT  - Insulin
OT  - Ion channels
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2024/02/15 18:42
MHDA- 2024/03/25 06:42
PMCR- 2024/02/15
CRDT- 2024/02/15 12:04
PHST- 2023/04/19 00:00 [received]
PHST- 2024/02/08 00:00 [accepted]
PHST- 2024/03/25 06:42 [medline]
PHST- 2024/02/15 18:42 [pubmed]
PHST- 2024/02/15 12:04 [entrez]
PHST- 2024/02/15 00:00 [pmc-release]
AID - 171609 [pii]
AID - 10.1172/jci.insight.171609 [doi]
PST - epublish
SO  - JCI Insight. 2024 Feb 15;9(6):e171609. doi: 10.1172/jci.insight.171609.