PMID- 22564773
OWN - NLM
STAT- MEDLINE
DCOM- 20130418
LR  - 20221207
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 14
IP  - 10
DP  - 2012 Oct
TI  - Effects of saxagliptin and sitagliptin on glycaemic control and pancreatic beta-cell 
      mass in a streptozotocin-induced mouse model of type 2 diabetes.
PG  - 918-26
LID - 10.1111/j.1463-1326.2012.01619.x [doi]
AB  - AIMS: We examined the effects of the oral dipeptidyl peptidase-4 (DPP-4) 
      inhibitor saxagliptin on glycaemic control and pancreatic beta-cell mass and 
      morphology in a mouse model of type 2 diabetes mellitus (T2DM). METHODS: Male 
      C57BL/6 mice (n = 12/group) aged 4 to 6 weeks and weighing >15 g received a 
      high-fat diet throughout this 45-day study. After a 7-day handling period, 
      baseline levels of plasma glucose, plasma insulin and glycated haemoglobin 
      (HbA1c) were assessed. Animals were allocated to one of six groups: compound 
      vehicle control, intraperitoneal streptozotocin (STZ, 50 mg/kg)-treated control 
      and saxagliptin (10 mg/kg) or sitagliptin (10 mg/kg, positive control) initiated 
      7 days before or 1 day after STZ administration. Endpoints included changes in 
      body weight, food and water consumption, glucose tolerance (approximately 3 weeks 
      post-STZ), fasting glucose and HbA1c and immunohistochemical analyses of the 
      pancreas. RESULTS: Body weight, weight gain and food intake were reduced in STZ 
      versus control mice. DPP-4 inhibitor treatment did not affect these changes, but 
      the increase in water intake observed post-STZ administration was significantly 
      attenuated with DPP-4 inhibitors whether initiated before or after STZ injury. 
      Small but significant improvements in glycaemic control were observed with DPP-4 
      inhibitors versus the STZ control. Improved beta-cell mass and morphology were 
      observed with saxagliptin given pre- or post-STZ and sitagliptin given post-STZ. 
      CONCLUSIONS: Saxagliptin mitigated damage to beta-cells and improved glycaemic 
      control in this mouse model of T2DM.
CI  - (c) 2012 Blackwell Publishing Ltd.
FAU - Poucher, S M
AU  - Poucher SM
AD  - CVGI Discovery iMED, AstraZeneca Pharmaceuticals, Macclesfield, UK. 
      Simon.Poucher@astrazeneca.com
FAU - Cheetham, S
AU  - Cheetham S
FAU - Francis, J
AU  - Francis J
FAU - Zinker, B
AU  - Zinker B
FAU - Kirby, M
AU  - Kirby M
FAU - Vickers, S P
AU  - Vickers SP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120528
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptides)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Pyrazines)
RN  - 0 (Triazoles)
RN  - 9GB927LAJW (saxagliptin)
RN  - PJY633525U (Adamantane)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
SB  - IM
MH  - Adamantane/*analogs & derivatives/pharmacokinetics/pharmacology
MH  - Animals
MH  - Blood Glucose/drug effects/*metabolism
MH  - Body Weight
MH  - Diabetes Mellitus, Experimental
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy/pathology
MH  - Diet, High-Fat
MH  - Dipeptides/pharmacokinetics/*pharmacology
MH  - Drinking
MH  - Eating
MH  - Glucose Tolerance Test
MH  - Glycated Hemoglobin/drug effects/*metabolism
MH  - Hypoglycemic Agents/pharmacokinetics/*pharmacology
MH  - Immunohistochemistry
MH  - Insulin-Secreting Cells/drug effects/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pyrazines/pharmacokinetics/*pharmacology
MH  - Sitagliptin Phosphate
MH  - Triazoles/pharmacokinetics/*pharmacology
EDAT- 2012/05/09 06:00
MHDA- 2013/04/20 06:00
CRDT- 2012/05/09 06:00
PHST- 2011/11/16 00:00 [received]
PHST- 2011/12/21 00:00 [revised]
PHST- 2012/05/02 00:00 [accepted]
PHST- 2012/05/09 06:00 [entrez]
PHST- 2012/05/09 06:00 [pubmed]
PHST- 2013/04/20 06:00 [medline]
AID - 10.1111/j.1463-1326.2012.01619.x [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2012 Oct;14(10):918-26. doi: 
      10.1111/j.1463-1326.2012.01619.x. Epub 2012 May 28.