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Long-term preoperative glycemic control restored the perioperative neutrophilic phagocytosis in diabetic mice.
Daichi Fujimoto
Kobe University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9864-9910
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Endocrine Disorders.
BACKGROUND: The risk of surgical site infection has been reported to be higher in patients with poorly controlled diabetes. Since chronic hyperglycemia impairs neutrophil functions, preoperative glycemic control may restore neutrophil function. However, long-term insulin therapy may lead to a delay in surgery, which may be a problem, especially in cancer surgery. It is therefore unfortunate that there have been few studies in which the optimal duration of perioperative glycemic control for diabetes with chronic hyperglycemia was investigated. Therefore, we investigated the effects of preoperative long-term insulin therapy and short-term insulin therapy on perioperative neutrophil functions in diabetic mice with chronic hyperglycemia.
METHODS: Five-week-old male C57BL/6J mice were divided into four groups (Untreated (Diabetes Mellitus: DM), Short-term (DM), Long-term (DM), and Non-diabetic groups). Diabetes was established by administrating repeated low-dose streptozotocin. The Short-term (DM)group received insulin therapy for 6 hours before the operation and the Long-term (DM)group received insulin therapy for 5 days before the operation. The Untreated (DM) group and the Non-diabetic group did not receive insulin therapy. At 14 weeks of age, abdominal surgery with intestinal manipulation was performed in all four groups. We carried out a phagocytosis assay with fluorescent microspheres and a reactive oxygen species (ROS) production assay with DCFH-DA (2’,7’-dichlorodihydrofluorescein diacetate) before and 24 hours after the operation using FACSVerse™ with BD FACSuite™ software.
RESULTS: Blood glucose was lowered by insulin therapy in the Short-term (DM) and Long-term (DM) groups before the operation. Neutrophilic phagocytosis activities before and after the operation were significantly restored in the Long-term (DM) group compared with those in the Untreated (DM) group (before: p = 0.0008, after: p = 0.0005). However, they were not significantly restored in the Short-term (DM) group. Neutrophilic ROS production activities before and after the operation were not restored in either the Short-term (DM) group or Long-term (DM) group.
CONCLUSIONS: Preoperative and postoperative phagocytosis activities are restored by insulin therapy for 5 days before the operation but not by insulin therapy for 6 hours before the operation.
Keywords
Diabetes mellitus, Duration of preoperative glycemic control, Surgery, Neutrophil, phagocytosis, reactive oxygen species, mice
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CURRENT STATUS: Published
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Posted 16 Jun, 2020
No comments provided
Editorial decision: Major revision
On 27 Apr, 2020
Review #2 received
Received 24 Apr, 2020
Review #1 received
Received 20 Apr, 2020
Reviewer #2 agreed
On 08 Apr, 2020
Reviewer #1 agreed
On 31 Mar, 2020
Reviewers invited
Invitations sent on 28 Mar, 2020
First submitted
On 22 Mar, 2020
Editor assigned
On 22 Mar, 2020
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On 21 Mar, 2020
Editor invited
On 21 Mar, 2020
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Subject Areas
Endocrinology & Metabolism
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This preprint is under consideration at BMC Endocrine Disorders. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Long-term preoperative glycemic control restored the perioperative neutrophilic phagocytosis in diabetic mice.
Daichi Fujimoto
Kobe University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9864-9910
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 16 Jun, 2020
No comments provided
Editorial decision: Major revision
On 27 Apr, 2020
Review #2 received
Received 24 Apr, 2020
Review #1 received
Received 20 Apr, 2020
Reviewer #2 agreed
On 08 Apr, 2020
Reviewer #1 agreed
On 31 Mar, 2020
Reviewers invited
Invitations sent on 28 Mar, 2020
First submitted
On 22 Mar, 2020
Editor assigned
On 22 Mar, 2020
Submission checks complete
On 21 Mar, 2020
Editor invited
On 21 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Endocrinology & Metabolism
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Endocrine Disorders.
BACKGROUND: The risk of surgical site infection has been reported to be higher in patients with poorly controlled diabetes. Since chronic hyperglycemia impairs neutrophil functions, preoperative glycemic control may restore neutrophil function. However, long-term insulin therapy may lead to a delay in surgery, which may be a problem, especially in cancer surgery. It is therefore unfortunate that there have been few studies in which the optimal duration of perioperative glycemic control for diabetes with chronic hyperglycemia was investigated. Therefore, we investigated the effects of preoperative long-term insulin therapy and short-term insulin therapy on perioperative neutrophil functions in diabetic mice with chronic hyperglycemia.
METHODS: Five-week-old male C57BL/6J mice were divided into four groups (Untreated (Diabetes Mellitus: DM), Short-term (DM), Long-term (DM), and Non-diabetic groups). Diabetes was established by administrating repeated low-dose streptozotocin. The Short-term (DM)group received insulin therapy for 6 hours before the operation and the Long-term (DM)group received insulin therapy for 5 days before the operation. The Untreated (DM) group and the Non-diabetic group did not receive insulin therapy. At 14 weeks of age, abdominal surgery with intestinal manipulation was performed in all four groups. We carried out a phagocytosis assay with fluorescent microspheres and a reactive oxygen species (ROS) production assay with DCFH-DA (2’,7’-dichlorodihydrofluorescein diacetate) before and 24 hours after the operation using FACSVerse™ with BD FACSuite™ software.
RESULTS: Blood glucose was lowered by insulin therapy in the Short-term (DM) and Long-term (DM) groups before the operation. Neutrophilic phagocytosis activities before and after the operation were significantly restored in the Long-term (DM) group compared with those in the Untreated (DM) group (before: p = 0.0008, after: p = 0.0005). However, they were not significantly restored in the Short-term (DM) group. Neutrophilic ROS production activities before and after the operation were not restored in either the Short-term (DM) group or Long-term (DM) group.
CONCLUSIONS: Preoperative and postoperative phagocytosis activities are restored by insulin therapy for 5 days before the operation but not by insulin therapy for 6 hours before the operation.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6