Mouse models created to study the pathophysiology of Type 2 diabetes

LeRoith, Derek; Гаврилова, Оксана

doi:10.1016/j.biocel.2005.01.019

Cited by 38 publications

(30 citation statements)

References 39 publications

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“…In most cases, IIS receptors, IIS ligands, or both are represented by multigene families. In mice, where this has been examined in most detail, family members have both distinct and overlapping roles in regulating animal physiology [reviewed in (7,42)]. Insulin-like activities were identified in invertebrates, including Drosophila, many years ago (43).…”

Section: Control Of Growth and Metabolism By Iis Is Evolutionarily Comentioning

confidence: 99%

Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities

Zhang

Liu

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

173

164

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Insulin/Insulin-like growth factor signaling regulates homeostasis and growth in mammals, and is implicated in diseases from diabetes to cancer. In Drosophila melanogaster, as in other invertebrates, multiple Insulin-Like Peptides (DILPs) are encoded by a family of related genes. To assess DILPs' physiological roles, we generated small deficiencies that uncover single or multiple dilps, generating genetic loss-of-function mutations. Deletion of dilps1-5 generated homozygotes that are small, severely growth-delayed, and poorly viable and fertile. These animals display reduced metabolic activity, decreased triglyceride levels and prematurely activate autophagy, indicative of ''starvation in the midst of plenty,'' a hallmark of Type I diabetes. Furthermore, circulating sugar levels are elevated in Df [dilp1-5] homozygotes during eating and fasting. In contrast, Df[dilp6] or Df[dilp7] animals showed no major metabolic defects. We discuss physiological differences between mammals and insects that may explain the unexpected survival of lean, 'diabetic' flies.diabetes ͉ DILP ͉ Drosophila insulin receptor ͉ insect physiology ͉ trehalose

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Section: Control Of Growth and Metabolism By Iis Is Evolutionarily Comentioning

confidence: 99%

Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities

Zhang

Liu

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

173

164

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“…Insulin-sensitive tissues, such as liver, fat, and muscle are typical involved in regulating whole body fuel metabolism (LeRoith and Gavrilova, 2006). Although the precise mechanisms by which insulin activates glycogen synthase remain unknown, numerous studies have suggested that the activation of Phosphoinositide 3-kinase (PI3K) by insulin may be a critical step.…”

Section: Introductionmentioning

confidence: 99%

MDG-1, a polysaccharide from Ophiopogon japonicus exerts hypoglycemic effects through the PI3K/Akt pathway in a diabetic KKAy mouse model

Wang

De-sheng

et al. 2012

Journal of Ethnopharmacology

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“…Insulin tolerance tests were performed after a 6-h fast. Blood glucose was measured before and after (10,20,30, and 60 min) an intraperitoneal injection of insulin (0.75 units/kg). Values are expressed relative to basal (6-h fast) blood glucose.…”

Section: Methodsmentioning

confidence: 99%

“…Glucose tolerance tests were performed in nondiabetic mice after an overnight (16 h) fast. Blood glucose levels were measured (OneTouch Ultra) before and after (10,20,30,60, 120, and 180 min) an intraperitoneal injection of D-glucose (1 g/kg). Insulin tolerance tests were performed after a 6-h fast.…”

Section: Methodsmentioning

confidence: 99%

Leptin Deficiency Unmasks the Deleterious Effects of Impaired Peroxisome Proliferator–Activated Receptor γ Function (P465L PPARγ) in Mice

et al. 2006

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Peroxisome proliferator-activated receptor (PPAR)␥ is a key transcription factor facilitating fat deposition in adipose tissue through its proadipogenic and lipogenic actions. Human patients with dominant-negative mutations in PPAR␥ display lipodystrophy and extreme insulin resistance. For this reason it was completely unexpected that mice harboring an equivalent mutation (P465L) in PPAR␥ developed normal amounts of adipose tissue and were insulin sensitive. This finding raised important doubts about the interspecies translatability of PPAR␥-related findings, bringing into question the relevance of other PPAR␥ murine models. Here, we demonstrate that when expressed on a hyperphagic ob/ob background, the P465L PPAR␥ mutant grossly exacerbates the insulin resistance and metabolic disturbances associated with leptin deficiency, yet reduces whole-body adiposity and adipocyte size. In mouse, coexistence of the P465L PPAR␥ mutation and the leptin-deficient state creates a mismatch between insufficient adipose tissue expandability and excessive energy availability, unmasking the deleterious effects of PPAR␥ mutations on carbohydrate metabolism and replicating the characteristic clinical symptoms observed in human patients with dominant-negative PPAR␥ mutations. Thus, adipose tissue expandability is identified as an important factor for the development of insulin resistance in the context of positive energy balance.

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Mouse models created to study the pathophysiology of Type 2 diabetes

Cited by 38 publications

References 39 publications

Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities

Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities

MDG-1, a polysaccharide from Ophiopogon japonicus exerts hypoglycemic effects through the PI3K/Akt pathway in a diabetic KKAy mouse model

Leptin Deficiency Unmasks the Deleterious Effects of Impaired Peroxisome Proliferator–Activated Receptor γ Function (P465L PPARγ) in Mice

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