PMID- 35477124
OWN - NLM
STAT- MEDLINE
DCOM- 20220602
LR  - 20220705
IS  - 1879-0739 (Electronic)
IS  - 0271-5317 (Linking)
VI  - 103
DP  - 2022 Jul
TI  - Lactoferrin improves hepatic insulin resistance and pancreatic dysfunction in 
      high-fat diet and streptozotocin-induced diabetic mice.
PG  - 47-58
LID - S0271-5317(22)00027-6 [pii]
LID - 10.1016/j.nutres.2022.03.011 [doi]
AB  - Lactoferrin (Lf) is an iron-binding glycoprotein with potentially beneficial 
      biological functions. However, the interaction between Lf and type 2 diabetes 
      mellitus (T2DM) remains unclear. We hypothesized that Lf would improve hepatic 
      insulin resistance and pancreatic dysfunction in diabetic mice. Male C57BL/6J 
      mice were fed a high-fat diet for 15 weeks and injected with streptozotocin (STZ) 
      for 5 consecutive days to establish a T2DM model. One week after STZ injection, 
      mice with >/=11.1 mmol/L fasting blood glucose concentration were considered T2DM 
      mice. These mice received 0.5% or 2% Lf solution for another 12 weeks. 
      Biochemical parameters were measured, and histopathological examination of the 
      pancreas and liver was performed. Hepatic protein expression related to the 
      insulin signalling pathway was also assessed. Diabetic mice showed insulin 
      resistance and abnormal glucolipid metabolism. Lf decreased serum concentrations 
      of glycated serum protein, fasting insulin, cholesterol, and triglyceride and 
      increased liver insulin sensitivity. Hematoxylin-eosin staining showed that Lf 
      reversed the abnormal pancreatic islets of diabetic mice. Lf improved pancreatic 
      dysfunction by reducing oxidative stress and inflammation responses. Furthermore, 
      Lf upregulated the protein expression of insulin receptor, insulin receptor 
      substrate-1, glucose transporter 4, phosphor phosphatidylinositol 
      3-kinase/phosphatidylinositol 3-kinase (PI3K), and phosphor protein kinase 
      B/protein kinase B (AKT) in the liver. This study indicated that Lf 
      supplementation improved hepatic insulin resistance and pancreatic dysfunction, 
      possibly by regulating the PI3K/AKT signaling pathway in T2DM mice.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Du, Yafang
AU  - Du Y
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Soochow 
      University, Suzhou, 215123, China; Department of Clinical Nutrition, Children's 
      Hospital of Zhejiang University School of Medicine, Hangzhou, China.
FAU - Li, Deming
AU  - Li D
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Soochow 
      University, Suzhou, 215123, China.
FAU - Chen, Jingsi
AU  - Chen J
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Soochow 
      University, Suzhou, 215123, China.
FAU - Li, Yun-Hong
AU  - Li YH
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Soochow 
      University, Suzhou, 215123, China.
FAU - Zhang, Zixiang
AU  - Zhang Z
AD  - Department of General Surgery, the First Affiliated Hospital of Soochow 
      University, Suzhou, 215006, China; State Key Laboratory of Radiation Medicine and 
      Protection, School of Radiation Medicine and Protection, Soochow University, 
      Suzhou 215123, China.
FAU - Hidayat, Khemayanto
AU  - Hidayat K
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Soochow 
      University, Suzhou, 215123, China.
FAU - Wan, Zhongxiao
AU  - Wan Z
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Soochow 
      University, Suzhou, 215123, China.
FAU - Xu, Jia-Ying
AU  - Xu JY
AD  - State Key Laboratory of Radiation Medicine and Protection, School of Radiation 
      Medicine and Protection, Soochow University, Suzhou 215123, China.
FAU - Qin, Li-Qiang
AU  - Qin LQ
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Soochow 
      University, Suzhou, 215123, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220327
PL  - United States
TA  - Nutr Res
JT  - Nutrition research (New York, N.Y.)
JID - 8303331
RN  - 0 (Insulin)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.21.- (Lactoferrin)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Experimental/drug therapy
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Diet, High-Fat/adverse effects
MH  - Insulin
MH  - *Insulin Resistance
MH  - Lactoferrin/adverse effects/metabolism
MH  - Liver/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pancreas/metabolism
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Streptozocin/adverse effects/metabolism
OTO - NOTNLM
OT  - Insulin resistance
OT  - Lactoferrin
OT  - Pancreas
OT  - Type 2 diabetes mellitus
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/04/28 06:00
MHDA- 2022/06/03 06:00
CRDT- 2022/04/27 20:09
PHST- 2021/09/25 00:00 [received]
PHST- 2022/03/16 00:00 [revised]
PHST- 2022/03/20 00:00 [accepted]
PHST- 2022/04/28 06:00 [pubmed]
PHST- 2022/06/03 06:00 [medline]
PHST- 2022/04/27 20:09 [entrez]
AID - S0271-5317(22)00027-6 [pii]
AID - 10.1016/j.nutres.2022.03.011 [doi]
PST - ppublish
SO  - Nutr Res. 2022 Jul;103:47-58. doi: 10.1016/j.nutres.2022.03.011. Epub 2022 Mar 
      27.