Abstract
AimsContinuous blood glucose monitoring, especially long-term and remote, in diabetic patients orresearch is very challenging. Nonhuman primate (NHP) is an excellent model for metabolic research,because NHPs can naturally develop Type 2 diabetes mellitus (T2DM) similarly to humans. This study was to investigate blood glucose changes in conscious, moving-free cynomolgus monkeys (Macaca fascicularis) during circadian, meal, stress and drug exposure.Materials and methodsBlood glucose, body temperature and physical activities were continuously and simultaneously recorded by implanted HD-XG telemetry device for up to 10 weeks.Results and discussionBlood glucose circadian changes in normoglycemic monkeys significantly differed from that in diabetic animals. Postprandial glucose increase was more obvious after afternoon feeding. Moving a monkey from its housing cage to monkey chair increased blood glucose by 30% in both normoglycemic and diabetic monkeys. Such increase in blood glucose declined to the pre-procedure level in 30 min in normoglycemic animals and >2 h in diabetic monkeys. Oral gavage procedure alone caused hyperglycemia in both normoglycemic and diabetic monkeys. Intravenous injection with the stress hormones, angiotensin II (2 μg/kg) or norepinephrine (0.4 μg/kg), also increased blood glucose level by 30%. The glucose levels measured by the telemetry system correlated significantly well with glucometer readings during glucose tolerance tests (ivGTT or oGTT), insulin tolerance test (ITT), graded glucose infusion (GGI) and clamp.ConclusionOur data demonstrate that the real-time telemetry method is reliable for monitoring blood glucose remotely and continuously in conscious, stress-free, and moving-free NHPs with the advantages highly valuable to diabetes research and drug discovery.
Highlights
Crown Bioscience, Inc., Taicang, Jiangsu Province, The People’s Republic of ChinaData Sciences International, St
This study investigated the real-time changes of blood glucose during circadian, meal, stress procedures, and drug exposures by the modified HD-XG transmitter device in conscious, moving-free cynomolgus monkeys (Macaca fascicularis) with or without diabetes
When blood glucose stabilized for approximately 30 min via observation of HD-XG glucose signals, the glucose solution (0.25 g/kg = 0.5 mL/kg of 50% dextrose) was intravenously infused via one cephalic vein within 30 s, and the system was flushed with 5 mL heparinized saline to push in the residual glucose
Summary
Crown Bioscience, Inc., Taicang, Jiangsu Province, The People’s Republic of China. Chronically dysfunctional carbohydrate metabolism results in diabetes due to a relative deficiency of insulin. Using implanted telemetry device for continuous glucose monitoring has been very limited in biomedical research, especially in large animals. The conventional ways, such as handheld glucometer, clinical chemistry analyzer, or analox analyzer, are generally used for blood glucose measurement. The HD-XG implantable glucose device (Data Sciences International, Saint Paul, MN, USA) provides continuous measurement of blood glucose, temperature, and locomotor activity for up to 2 months in rodents [12]. This study investigated the real-time changes of blood glucose during circadian, meal, stress procedures, and drug exposures by the modified HD-XG transmitter device in conscious, moving-free cynomolgus monkeys (Macaca fascicularis) with or without diabetes. Signal strength variation due to physical activity of the subject provided a continuous real-time activity count as calculated in the DEM/MX2 (Data Sciences International, Saint Paul, MN, USA)
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