Simple Continuous Glucose Monitoring in Freely Moving Mice

Summary

Here, we describe a simple method to implant a commercial continuous glucose monitor designed for patients onto mice and provide the scripts to analyze the results.

Abstract

Mice are a common model organism used to study metabolic diseases such as diabetes mellitus. Glucose levels are typically measured by tail-bleeding, which requires handling the mice, causes stress, and does not provide data on freely behaving mice during the dark cycle. State-of-the-art continuous glucose measurement in mice requires inserting a probe into the aortic arch of the mouse, as well as a specialized telemetry system. This challenging and expensive method has not been adopted by most labs. Here, we present a simple protocol involving the utilization of commercially available continuous glucose monitors used by millions of patients to measure glucose continuously in mice as a part of basic research. The glucose-sensing probe is inserted into the subcutaneous space in the back of the mouse through a small incision to the skin and is held in place tightly using a couple of sutures. The device is sutured to the mouse skin to ensure it remains in place. The device can measure glucose levels for up to 2 weeks and sends the data to a nearby receiver without any need to handle the mice. Scripts for the basic data analysis of glucose levels recorded are provided. This method, from surgery to computational analysis, is cost-effective and potentially very useful in metabolic research.

Introduction

Diabetes mellitus (DM) is a devastating disease characterized by high blood glucose levels. Type 1 DM can be a result of an autoimmune attack on the insulin-producing beta cells in the pancreas. Type 2 DM and gestational DM, on the other hand, are characterized by a failure of the beta cells to secrete sufficient insulin in response to a rise in glucose levels¹. The mouse is a common model organism used to study DM since it has similar physiology, and its normal glucose levels are close to those of humans. Furthermore, specific mouse strains may develop DM due to mutations in key signaling pathways or following exposure to....

Protocol

The experiments were approved by the Hebrew University's Institutional Animal Care and Use Committee (IACUC).

NOTE: All tools must be sterilized, and handling of the cannula must be performed using a sterile technique. The protocol below is fine-tuned to a specific CGM. The protocol can be adapted to other CGMs.

1. Analgesic administration before the procedure

1. Administer 5% dextrose and 0.45% saline with meloxicam at 5 mg/kg body weight subcutaneously.

2. Anesthesia administration

1. Place the mouse in the induction chamber,....

Results

Surgical outcome
Results from eight HSD:ICR mice (aged 8 weeks) fed a high-fat high-sucrose diet (HFHS) for 18 weeks and five lean HSD:ICR mice (aged 12 weeks) are shown. The device we used stores data for up to 8 h. Access to the local animal facility was restricted to 07:00-19:00, thus prohibiting data collection during the late P.M. hours, when the mice are active. The mice were, therefore, placed in a room with reverse lighting for 7 days before the surgical procedure, with dark hours between 8:3.......

Discussion

This protocol offers a simple, inexpensive method to monitor glucose levels in mice that does not require challenging microsurgery and does not involve bleeding or handling the mice. The method is easy to implement in every facility and does not cause mortality, pain, or excessive discomfort to the mice. The most critical step in the protocol is inserting the cannula of the glucose sensor under the skin of the mouse. The addition of a few sutures allows the cannula to stay in place for a longer time. The sensors are smal.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
2%  Chlorhexidine Gluconate and 70%  Isopropyl Alcohol	3M	ID 7000136290
5% Dextrose and 0.45% Sodium Chloride Injection, USP	Braun	L6120
Castroviejo needle holder	FST	12061-02
Extra Fine Bonn scissors	FST	14084-08
FreeStyle Libre 1 reader	Abbott	ART27543
FreeStyle Libre sensor	Abbott	ART36687
FreeStyle Libre sensor applicator	Abbott	ART36787
Gauze pads	Sion medical	PC912017
Graefe Forceps	FST	11052-10
Hair Removal Cream	Veet	3116523
High-fat high-sucrose diet	Envigo Teklad diets	TD.08811
Isoflurane, USP Terrell	Piramal	26675-46-7
Meloxicam 5 mg/mL	Chanelle Pharma	08749/5024
MiniARCO Clipper kit	Moser	CL8787-KIT
PROLENE Polypropylene Suture 5-0	Ethicon	8725H
Puralube Opthalmic Ointment	Perrigo	574402511
Q-tips	B.H.W	271676
SomnoSuite Low-Flow Anesthesia System	Kent Scientific	SOMNO