What do we know about the diagnosis of feline prediabetes? A review of current perspectives

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Diabetes mellitus (DM) is the second most common endocrine disease reported for the domestic cat, following hyperthyroidism. DM has a significant impact on the welfare of affected animals and their domestic environment. It is estimated that 30% of affected cats are euthanized within the first year after diagnosis, which reveals the profound impact of this disease on the quality of life and well-being of animals and owners. Hence, the search for early biomarkers of prediabetes or subclinical diabetes, although needed, has not been fully achieved. This scoping review was assembled from an online search in major scientific databases, from which a total of 681 articles were chosen. From this pool, twenty-three articles aligned with the study objectives and were included in the review. Levels of fasting blood glucose, fructosamine, triglycerides, albumin, and insulin have been identified in the literature as parameters reflecting an altered glucose metabolism, while predisposal risk factors for cats also exist. However, a practical and rigorous early diagnostic tool with markers and methods to enable early detection of prediabetes is not yet available.

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  • Research Article
  • 10.24126/jobrc.2015.9.2.440
Study the Relationship Between Obesity and Fertility in Diabetic Iraqi Men
  • Jun 1, 2015
  • Journal of Biotechnology Research Center
  • Dunia Tahseen Nema Al-Aridhi + 1 more

The aim of the present study is to investigate the relationship between obesity and fertility in Iraqidiabetic men whose body mass index (BMI) more than 25Kg/m2, and compare the results with controlgroup corresponding age and BMI. Forty samples of men semen's were divided into two groups with andwithout diabetes and each group subdivided into two subgroups according to BMI. The parameters thatmeasured in this study are( glucose, insulin and lipid profile in fasting state) also (testosterone, prolactin,alkaline phosphatase) were measured for each of four subgroups [controls(I, II) and diabetes(III, IV)].Semen's analysis included (sperm concentration in ml, total count per ejaculate and viability). In diabeticsubgroup (III) the mean levels of fasting blood glucose, insulin, cholesterol and triglycerides weresignificantly elevated, while significantly decrease in testosterone, prolactin, high density lipoproteinscholesterol, alkaline phosphatase and total sperm count but there were no significant difference in totalcholesterol, the sperm concentration and viability as compared with control subgroup(I). In diabeticsubgroup (IV) the mean levels of fasting blood (glucose, insulin, cholesterol and triglycerides) weresignificantly elevated, while significantly decrease in (testosterone, prolactin, high density lipoproteinscholesterol, alkaline phosphatase, sperm concentration, viability and total sperm count) but there were nosignificant difference in fasting (insulin and high density lipoproteins- cholesterol) as compared withcontrol subgroup(II). In diabetic subgroup(III) the mean of BMI and the mean levels of fasting blood(glucose, total cholesterol and triglycerides) significantly elevated, while there were significantly decreasein(testosterone, alkaline phosphatase, sperm concentration, viability and total sperm count but there wereno significant difference in fasting (insulin, high density lipoproteins- cholesterol) and prolactin, ascompared with diabetic subgroup(IV). For all the above biochemical parameters investigated we canconclude that there is inverse- relationship between obesity and fertility which increase in the presence ofdiabetes.

  • Research Article
  • Cite Count Icon 74
  • 10.1016/s0002-8703(99)70256-5
Association of fasting blood sugar level, insulin level, and obesity with left ventricular mass in healthy children and adolescents: The Bogalusa Heart Study
  • Jul 1, 1999
  • American heart journal
  • Elaine M Urbina + 4 more

Association of fasting blood sugar level, insulin level, and obesity with left ventricular mass in healthy children and adolescents: The Bogalusa Heart Study

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  • Cite Count Icon 5
  • 10.1089/lrb.2019.0072
Is There a Relationship Between Insulin Resistance and Breast Cancer-Related Lymphedema? A Preliminary Study.
  • Mar 23, 2021
  • Lymphatic Research and Biology
  • Pınar Doruk Analan + 1 more

Background: High blood insulin levels, insulin resistance (IR), and obesity are components of metabolic syndrome (MetS). The literature has indicated a high risk of breast cancer in patients with MetS. However, no studies have been conducted evaluating the relationship between breast cancer-related lymphedema (BCRL), one of the most frequently encountered postbreast cancer treatment conditions, and IR. Therefore, the aim of this study was to evaluate whether there is a relationship between BCRL and IR. Methods and Results: A total of 28 patients diagnosed with breast carcinoma were included in this preliminary study. Patients were divided into BCRL (n = 15; mean age: 55.2 ± 11.2 years) and non-BCRL (control) groups (n = 13; mean age: 55.17 ± 6.57 years). Body mass index (BMI), waist and hip circumference, and fasting blood glucose and blood insulin levels of all patients were recorded. The Homeostasis Model Assessment (HOMA) test was used for the calculation of IR measurement with a value of 2.5 taken as an indicator of IR. Parameters were compared between groups. BMI, waist circumference measurements, blood insulin, and HOMA-IR levels were statistically significantly higher in the BCRL group than the control group (p < 0.05). HOMA-IR values >2.5 were found in 14 patients in the BCRL group. In the control group, only three patients had IR based on HOMA-IR criteria (p = 0.000). Hip circumference measurements and fasting blood glucose levels were similar between the groups (p > 0.05). Conclusions: BCRL appears to be associated with waist circumference, fasting blood insulin level, and HOMA-IR levels. In routine clinical practice, evaluation of IR may be important in the follow-up of this patient population.

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  • Cite Count Icon 1
  • 10.53350/pjmhs22166403
Study of Irisin Level Hormone and Some Biochemical Parameters in Iraqi Diabetic Type 2 without Hypothyroidism
  • Jun 29, 2022
  • Pakistan Journal of Medical and Health Sciences
  • Huda Amjad Hashim + 1 more

This case-control study's purpose is to investigate serum irisin. levels and their role in people with type 2 diabetes mellitus (T2DM) who don't have hypothyroidism. A total of 60 patients with T2DM were chosen as the) case group (based on the grounds for inclusion and exclusion, and a 1:1 ratio was determined based on the patients' inclusion rate. This cohort, which was created at the Medical City / Baghdad Teaching Hospital, consisted of adults aged 30 to 60. The control group consisted of 60 healthy volunteers of the same gender and age. Clinical data on the participants was collected in order to determine their medical history, BMI, fasting blood glucose (FBS), hemoglobin (HbA1c), insulin, and serum lipid levels. An enzyme-linked immunosorbent test was used to measure the amount of irisin in the blood (ELISA). The data was analyzed using SPSS 23.0 software. only one variable. The amount of irisin in the T2DM group was substantially higher than in the control group (12.77±2.236 ng /mL and 4.121±0.308 ng /mL, respectively, according to single factor analysis. BMI, fasting blood sugar (FBS), HbA1c, insulin, total cholesterol (TC), and triglyceride (TG) levels were all higher with statistically significant differences, the T2DM group outperformed the control group. Keywords: Irisin; Type 2 diabetic mellitus

  • Research Article
  • 10.36321/kjns.vi20152.2585
The Relevance of Adiponectin and Resistin Levels with Oxidative Stress in Insulin Resistant Type 2 Diabetes
  • Oct 12, 2015
  • Kufa Journal for Nursing Sciences
  • Fares Hassen Hassani

Objectives: The present study was designed to verify the changes of adiponectin and resistin with oxidativestress in insulin resistant in diabetes mellitus type 2. Methodology: To achieve this aim 60 patients with type 2 diabetes mellitus (24 male and 36 female ) of ages,53.9 ± 12.4 years in addition to 30 apparently healthy individuals (13 males and 17 females) were enrolled.The concentration of fasting blood glucose, triglyceride, insulin, adiponectin, resistin and malondialdehyde(MDA) levels were measured. Fasting insulin concentration, adiponectin and resistin was measured by enzymelinked immunosorbantassay( ELISA). Fasting blood glucose and triglyceride levels were determined byenzymatic methods. Malondialdehyde (MDA) levels were measured by spectrophotometeric methods . Insulinresistance was evaluated by four methods . Results: The results indicated that out of 60 patients, 49 (81%), 45 (75%), 33 (55%) and 32 (53%) wereinsulin resistant when they were evaluated by Homeostasis model assessment ( HOMA), Quantitative insulinsensitivity check index (QUICKI), McAuley's index (MCA) and fasting insulin(FI) indices respectively. The 49insulin resistant type 2 diabetic patients (IRP) that obtained through the HOMA method were assessed for thealteration in the levels adiponectin, resistin and MDA. The analysis of the data revealed a significant decrease ofadiponectin in the IRP group when compared with those of the insulin sensitive patients (ISP) and the controlgroups. Significant elevation of resistin levels were observed in the IRP group with respect to those of thecontrol groups. Conclusion: Insulin resistance was found to be significantly positively correlated with resistin, MDA andsignificantly negatively correlated with adiponectin levels in diabetic patients. Adiponectin exhibitedinsignificant negative correlation with resistin and significant negative correlation with MDA levels, while thelevel of resistin showed a significant positive correlation with MDA level in insulin resistant type 2 diabetics. Recommendations: A study on of the effect free fatty acid on the activity of insulin degrading enzymes in obeseindividual.

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  • Cite Count Icon 10
  • 10.13181/mji.v23i4.848
Prevention of insulin resistance with &lt;em&gt;Hibiscus sabdariffa&lt;/em&gt; Linn. extract in high-fructose fed rat
  • Jan 27, 2015
  • Medical Journal of Indonesia
  • Trinovita Andraini + 1 more

Background: Dyslipidemia and stress oxidative play an important role as the cause of insulin resistance. One herb that has potent antioxidant effect and may improve dyslipidemia is Hibiscus sabdariffa Linn. The aim of this study was to evaluate the effect of Hibiscus sabdariffa Linn. extract on fasting blood glucose level, fasting blood insulin level, and insulin resistance index (HOMA-IR) in high-fructose fed rat.Methods: This was an experimental study in 25 Sprague-Dawley rats which were administered with a high-fructose diet (10% ad libitum) and Hibiscus sabdariffa Linn. extract at a dose of 100, 200, and 400 mg/kgBW/d simultaneously for 5 weeks. At the end of study, fasting blood glucose level, fasting blood insulin level and insulin resistance index (HOMA-IR) were measured.Results: Fasting blood glucose, blood insulin, and HOMA-IR level of rats given high-fructose diet with Hibiscus sabdariffa Linn. at dose 100 mg/kgBW/d were not significantly different than the group of rats given only high-fructose fed. While at the dose of 400 mg/kgBW/d, they were significantly lower than the group given only high-fructose fed (4.84 mmol/L vs 6.11 mmol/L, 0.07 µU/L vs 0.3 µU/L, and 0.02 vs 0.08 respectively).Conclusion: Oral administration of Hibiscus sabdariffa Linn. could prevent the development of insulin resistance induced by high-fructose diet in the rat.

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  • 10.34011/jmp2k.v34i1.1846
KOMBINASI KACANG MERAH DAN KULIT KACANG HITAM PADA TIKUS WISTAR MODEL DIABETES MELITUS TIPE 2
  • Feb 19, 2024
  • Media Penelitian dan Pengembangan Kesehatan
  • Pratiwi Wulandari + 2 more

Type 2 Diabetes Mellitus (T2DM) is a metabolic disease that require pharmacological and non-pharmacological therapies. Comsuming functional foods that are high in antioxidants and fiber such as red beans and black beans beneficial to patients with T2DM. The study aimed to examine the effect of the combination of red beans (Phaseolus vulgaris L.) flour and black beans (Phaseolus vulgaris) coat extract on body weight, blood glucose, insulin level and pancreatic tissue of T2DM model rats. This randomized controlled trial involved 36 male Wistar rats divided into 6 groups consisted of non-diabetic rats (Group I) and nicotinamide-streptozotocin induced diabetic rats (Group II-VI). Group II was negative control; Group III-V were given a combination with the proportion of flavonoid/ fiber in each kgBW as follows: 22.5 mg/0.25 g; 45 mg/0.5 g; and 90 mg/1 g. Group VI was the positive control. Data on body weight, fasting blood glucose levels and insulin levels were analyzed using Two-Way Anova, while pancreatic histopathology scoring data used Kruskal-Wallis.There was a significant difference between the dose and duration of intervention on body weight, fasting blood glucose and insulin levels (p=0.001). The intervention groups showed there were no pancreatic histopathology change as good as the positive control (p&gt;0.05). The combination of flavonoids and fiber at a dose of 45 mg/0.5 g per kgBW was proven to gain weight, reduce fasting blood glucose levels, increase insulin levels and no pancreatic histopathology change in T2DM rats models as well as the postive control group.

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  • 10.30867/action.v9i1.1312
The effect of EKORMIN on rats with diabetes mellitus model: effectiveness on fasting blood glucose, MDA, and insulin levels
  • Mar 12, 2024
  • AcTion: Aceh Nutrition Journal
  • Siti Nurjana Kurniaty Tanaiyo + 2 more

Antioxidant use for additional diabetes mellitus therapy is growing, such as okra (Abelmoschus esculentus) and turmeric (Curcuma longa), which are rich in flavonoids and have beneficial effects on diabetes mellitus. This study aimed to determine the effects of okra turmeric extract (EKORMIN) on Fasting Blood Glucose (FBG), malondialdehyde (MDA), and insulin levels in diabetic rats. The research was conducted from December to January 2022 at PSPG UGM using experimental research with a pre-posttest-controlled group design. White male Wistar rats (n = 35) randomly grouped into five: negative control (STZ-NA), positive control (STZ-NA+metformin 1,8 mg/200 gBW), P1 (STZ-NA+EKORMIN low dose 130,5;110,5 mg/kgBW), P2 (STZ-NA+EKORMIN moderate dose 261;221 mg/kgBW), P3 (STZ-NA+EKORMIN high dose 522;442 mg/kgBW). The intervention lasted 14 days. Data analysis was performed using one-way analysis of variance statistical tests and post hoc follow-up tests. EKORMIN in all doses, EKORMIN reduced FBG and MDA levels and increased insulin levels (p&lt;0,05). P2 and P3 were not significantly different from the metformin (PG) group (p&gt;0,05). The decrease in FBG (-167,05±-2,8 vs -175,86±-1,4 mg/dL) and MDA levels (-6,32±0,33 vs -7,98±0,07 nmol/ml) P3 was higher than P2. Similarly for increased insulin levels (121,47±3,03 and 164,09±4,48 pg/ml). EKORMIN was effective in reducing FBG and MDA levels and increased insulin levels in diabetic rats. EKORMIN has antidiabetic effects and has potential for type 2 diabetes mellitus treatment.

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  • Cite Count Icon 26
  • 10.4314/ejhs.v26i5.2
Insulin Sensitivity and Plasma Glucose Response to Aerobic Exercise in Pregnant Women at Risk for Gestational Diabetes Mellitus.
  • Sep 19, 2016
  • Ethiopian Journal of Health Sciences
  • Heba Embaby + 2 more

Gestational diabetes mellitus (GDM) is one of the common complications that occur during pregnancy. Early intervention is essential to prevent the development of the disease in the non-pregnant state but also helpful in preventing the occurrence of GDM. The aim of the study was to assess the effect of aerobic exercises on insulin sensitivity and fasting plasma glucose level in pregnant women with risk for gestational diabetes mellitus. Forty multigravidae women between 20-24 weeks of gestation with risk for GDM were randomly selected (age range was 25-35 years), body mass index ranged from 30-35 kg/m2. Women were divided into two equal groups: intervention group (A), which followed an aerobic exercise program in the form of walking on treadmill, three times weekly until the end of 37 weeks of gestation in addition to diet control. Control group (B) which received diet control with usual care given by obstetricians and midwives. Evaluation of the women in both groups was carried out before and after treatment program through assessment of fasting blood glucose and insulin levels. There was a highly statistically significance decrease in fasting blood glucose level, fasting insulin level in both groups where the p value was 0.0001 favoring group (A). Moderate intensity of aerobic exercises were effective in reducing fasting blood glucose level and fasting insulin level in pregnant women with risk for gestational diabetes mellitus.

  • Research Article
  • Cite Count Icon 3
  • 10.1016/j.heliyon.2020.e03251
Tracking changes of the parameters of glucose-insulin homeostasis during the course of obesity in B6D2F1 mice
  • Jan 1, 2020
  • Heliyon
  • Sakineh Esmaeili Mohsen Abadi + 6 more

Tracking changes of the parameters of glucose-insulin homeostasis during the course of obesity in B6D2F1 mice

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  • 10.12047/j.cjap.5670.2019.031
Treatment of type 2 diabetes mellitus with the stem and leaf of blacktartary buckwheat and its effects on the pancreas and spleen
  • Feb 1, 2019
  • Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology
  • Wei Ling Xiang + 4 more

Treatment of type 2 diabetes mellitus with the stem and leaf of blacktartary buckwheat and its effects on the pancreas and spleen

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  • Research Article
  • 10.3329/imcjms.v14i1.47382
Association of visceral adiposity index with insulin resistance in adults with diabetes mellitus
  • Jun 5, 2020
  • IMC Journal of Medical Science
  • Sultana Parveen + 7 more

Background and objectives: Visceral adiposity is linked to excess morbidity and mortality and positively correlates with the risk of insulin resistance, type-2 diabetes mellitus, cardiovascular disease and premature death. The study was conducted to find out the relationship between visceral adiposity index (VAI) and homeostatic model assessment insulin resistance (HOMA-IR) in diabetes mellitus (DM).&#x0D; Materials and methods: This cross sectional study was carried out on adult population with and without DM. Waist circumference (WC) and body mass index (BMI) were measured. BMI of 25-29.9 kg/m2 and ≥30 kg/m2 was defined as overweight and obese respectively. HOMA-IR method was used to calculate insulin resistance (IR). Standard formula using BMI, WC, triglyceride (TG) and high density lipoprotein cholesterol (HDL-c) was used to calculate VAI. Blood was analyzed for fasting blood glucose (FBS), TG, HDL-c and insulin level.&#x0D; Results: A total of 439 individuals were included in the study of which 269 had DM and 170 were healthy volunteers and the mean age was 41.47±6.82 and 36.16±7.44 years respectively. Compared to healthy controls, a greater number of diabetics had high VAI (86.5% vs. 98.9%) and high IR (43.5% vs. 85.1%). We found the highest sensitivity and specificity at a cut-off of 2.23 of VAI while at 3.65 had the highest specificity. Insulin resistance was observed significantly higher in those with diabetes compared to control, both in case of normal and high VAI at all cut-offs of VAI. Among anthropometric parameters (WC, BMI and VAI), VAI had positive (r=0.21, p&lt;0.001) correlation with HOMA-IR than WC (r=0.10, p=0.043). Visceral fat was linearly related with insulin resistance (ß=0.18, p&lt;0.001). Area under the curve (AUC) (0.66) showed that VAI can discriminate HOMA-IR.&#x0D; Conclusion: There was a high rate of raised VAI in cases with DM. VAI had positive association with HOMA-IR in diabetes mellitus. Although weak, there was an acceptable discrimination between them.&#x0D; Ibrahim Med. Coll. J. 2020; 14(1): 5-12

  • Research Article
  • 10.3760/cma.j.issn.1001-9030.2011.03.017
Blood glucose-lowering effect of different types of anastomosis in gastrojejunostomy on type 2 diabetes mellitus in Goto-Kakizaki rats
  • Mar 8, 2011
  • Chinese journal of experimental surgery
  • Ya-Bin Jiao + 8 more

Objective To investigate the effect after gastrojejunostomy with different types of anastomosis in an animal model of nonobese type 2 diabetes.Methods Twenty-four Goto-Kakizaki rats randomly underwent one of the following procedures:gastric bypass with different types of anastomosis of Roux-en-Y ( n = 8),Billroth Ⅱ ( n = 8 ) or Billroth Ⅰ ( n = 8 ).Rats were observed for 24 weeks after surgery.Fasting blood glucose and insulin level were tested at 0,1,3,6,12,24 weeks and homeostasis model assessment of insulin resistance (HOMA-IR) was done.Results As compared with preoperation,fasting blood glucose levels,the fasting blood insulin level and the HOMA-IR level had no significant change in Billroth Ⅰ rats during the entire follow-up period ( P > 0.05).In both Roux-en-Y and Billroth Ⅱ groups,fasting blood glucose levels were significantly decreased as early as 1 week after surgery and then kept a similar level during the entire follow-up period (P<0.01 ).Twenty-four weeks after operation,the fasting blood glucose levels was declined from (12.56 ±2.97),(12.96 ±3.01) mmol/L to (7.87 ±0.75),(9.21 ± 1.53) mmol/L;the fasting blood insulin levels were similar during the entire follow-up period ( P >0.05 ).The HOMA-IR level was significantly decreased after surgery in both Roux-en-Y and Billroth Ⅱ groups during the follow-up period ( P<0.01 ).Twenty-four weeks after operation,the HOMA-IR level was declined from (11.92 ± 1.45),(12.69 ±2.03) to (6.66 ± 1.25),(7.97 ±0.68).Conclusion Billroth Ⅰ reconstruction after gastrectomy is not effective on diabetes control.Roux-en-Y and Billroth Ⅱ gastric bypass in a nonobese diabetic model were effective in terms of glucose control and improving insulin resistance.But Roux-en-Y gastric bypass seems to be more effective than Billroth Ⅱ gastric bypass on antidiabetes. Key words: Type 2 diabetes mellitus; Gastric bypass; Insulin resistance

  • Research Article
  • Cite Count Icon 50
  • 10.1093/oxfordjournals.aje.a009021
Cardiovascular risk factors in children from the Belgian province of Luxembourg. The Belgian Luxembourg Child Study.
  • Nov 1, 1996
  • American journal of epidemiology
  • M Guillaume + 4 more

The Province of Luxembourg is an area in Belgium with a high prevalence of risk factors for cardiovascular disease and non-insulin-dependent diabetes mellitus among adults. In the present study, children in the age groups 6-8, 8-10, and 10-12 years were selected at random from school classes (n = 1,028), with a participation rate of 70.3%. Anthropometric factors, blood pressure, and fasting blood glucose, plasma cholesterol, triglyceride, and insulin levels were measured in 1992. All anthropometric and metabolic variables increased with age, except for waist: hip circumference ratio in boys and cholesterol in girls. In the oldest group, girls who had passed menarche were taller and heavier and had greater skinfold, body mass index, insulin, and systolic blood pressure values but lower total cholesterol levels and waist: hip ratios than girls who had not passed menarche. Boys had lower skinfolds and higher waist: hip ratios than girls in all age groups, and were significantly shorter and lighter in the oldest age group. There was no difference in body mass index between the two sexes. Girls had higher triglyceride and insulin levels in the 10- to 12-year age group, lower blood glucose values in the 8-10 and 10-12 age groups, and lower diastolic blood pressures in the 8-10 age group. Obesity, blood glucose, triglycerides, insulin, and blood pressure were highly interrelated. Cholesterol, triglycerides, insulin, and blood pressure values were all among the highest of values previously reported in other studies. The deciles of body mass index above 50 appeared to be particularly elevated, suggesting that obesity, when present, was pronounced in this population of children. These findings suggest an accumulation of genetic susceptibility to cardiovascular disease and non-insulin-dependent diabetes mellitus in this stable, ethnically homogeneous, and rather isolated part of continental Europe.

  • Research Article
  • Cite Count Icon 1
  • 10.1111/liv.70306
ATP8B1 Deficiency Causes Phosphodiesterase 4-Mediated Glucagon Resistance and Impaired Gluconeogenesis in Mouse and Human Liver.
  • Aug 25, 2025
  • Liver international : official journal of the International Association for the Study of the Liver
  • Jung-Chin Chang + 18 more

Deficiency of the phospholipid transporter ATP8B1 causes infantile-onset progressive familial intrahepatic cholestasis type I (PFIC1). Pre-transplant PFIC1 patients often present with mild dyslipidaemia. This raises the possibility that PFIC1 patients, besides cholestasis, may also experience defects in glucose and lipid metabolism. In this study, we aimed to investigate the role of ATP8B1 in hepatic glucose and lipid metabolism using the Atp8b1G308V/G308V mutant mouse, a pre-clinical model of PFIC1. Atp8b1G308V/G308V and wild-type mice on normal chow were examined. Hepatic glucose metabolism was evaluated by oral glucose tolerance testing, quantification of fasting plasma glucose, insulin and lipids. Mechanistic studies were conducted in primary mouse hepatocytes (PMHs) and HepG2 cells overexpressing glucagon receptor (HepG2-GCGR). The findings in the mouse model were validated in pre-transplant livers from PFIC1 patients. Atp8b1G308V/G308V mice showed decreased levels of fasting blood glucose, triglycerides and insulin, indicating normal insulin sensitivity and impaired hepatic glucagon response. PMHs from Atp8b1G308V/G308V mice exhibited reduced glucagon-dependent cAMP levels and signalling and had increased expression of Pde4 isoforms. Rolipram-mediated PDE4 inhibition restored glucagon signalling. ATP8B1 knockdown HepG2-GCGR cells also showed increased PDE4D expression and impaired glucagon signalling. Liver tissue from PFIC1 patients exhibited elevated PDE4D and reduced p-CREB levels and very low glycogen content. ATP8B1 deficiency causes upregulation of PDE4D in the liver of Atp8b1G308V/G308V mice and PFIC1 patients. PDE4D-mediated glucagon resistance impairs gluconeogenesis and stimulates compensatory glycogenolysis in Atp8b1G308V/G308V mice and PFIC1 patients. Our study reveals novel metabolic insights of ATP8B1 deficiency in PFIC1 patients.

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