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2017 ; 7
(1
): 11906
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Time-dependent effects of ipragliflozin on behaviour and energy homeostasis in
normal and type 2 diabetic rats: continuous glucose telemetry analysis
#MMPMID28928461
Iuchi H
; Sakamoto M
; Matsutani D
; Suzuki H
; Kayama Y
; Takeda N
; Minamisawa S
; Utsunomiya K
Sci Rep
2017[Sep]; 7
(1
): 11906
PMID28928461
show ga
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs
that promote urinary glucose excretion. Conversely, they cause behavioural
changes, such as hyperphagia, that result in a positive energy balance. The
relationship between energy homeostasis and SGLT2 inhibitors-induced behavioural
changes remains unclear. Here we show that ipragliflozin, a SGLT2 inhibitor,
time-dependently affects behaviour and enhances energy expenditure in normal and
type 2 diabetic Goto-Kakizaki (GK) rats, using continuous glucose telemetry.
Alongside increased urinary glucose excretion, ipragliflozin increased total food
and water intakes in normal and GK rats. In normal rats, ipragliflozin treatment
acutely disturbed the circadian rhythms of food and water intakes, activity, and
body temperature. Subsequently, these rhythms gradually returned towards a normal
state. However, activity and body temperature remained suppressed. In GK rats,
ipragliflozin did not affect circadian rhythms. Blood glucose values assessed by
glucose telemetry were significantly reduced in both ipragliflozin-treated
groups. Despite these behavioural and glycaemic changes, ipragliflozin
significantly increased oxygen consumption during dark and light periods in both
groups. Ipragliflozin reduced body weight in normal rats only. Thus,
ipragliflozin decreases blood glucose beyond compensatory hyperphagia in normal
and GK rats, resulting in enhanced basal energy expenditure, despite acutely
altering circadian rhythms in normoglycaemic individuals.
|Animals
[MESH]
|Blood Glucose/*analysis
[MESH]
|Body Temperature/drug effects
[MESH]
|Circadian Rhythm/drug effects
[MESH]
|Diabetes Mellitus, Type 2/blood/*drug therapy/urine
[MESH]