Detection of insulin and insulin-like growth factors I and II in saliva and potential synthesis in the salivary glands of mice

Kerr, Micah; Lee, Annie; Wang, Pao-Li; Purushotham, Karnam R.; Chegini, Nasser; Yamamoto, Hideo; Humphreys‐Beher, Michael G.

doi:10.1016/0006-2952(95)00017-t

Cited by 64 publications

(48 citation statements)

References 38 publications

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“…Brown et al (35) demonstrated enhanced cutaneous wound closure after application of plateletderived growth factor and TGF-␣ to db/db diabetic mice but not with EGF. Like EGF, NGF and IGF-II are reduced in saliva, whereas IGF-I concentrations remain high in diabetic mice (10,26).…”

Section: Discussionmentioning

confidence: 99%

Reduced Oral Wound Healing in the NOD Mouse Model for Type 1 Autoimmune Diabetes and Its Reversal by Epidermal Growth Factor Supplementation

Nagy

Nagashima²,

Cha³

et al. 2001

Diabetes

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Using the NOD mouse, a model for type 1 diabetes, we examined how reduced concentrations of epidermal growth factor (EGF) in the saliva, after onset of type 1 diabetes, affect oral wound healing. Diabetic NOD/LtJ mice on insulin therapy, prediabetic NOD/LtJ, and ageand sex-matched BALB/cJ mice were given a cutaneous tongue punch and allowed to undergo normal healing. With diabetes onset and a reduction in saliva-derived growth factor levels, the rate of tongue wound healing was reduced compared with nondiabetic NOD/LtJ and healthy BALB/cJ mice. Addition of exogenous EGF to the drinking water did not accelerate the rate of healing in BALB/cJ or prediabetic NOD/LtJ; however, diabetic NOD/LtJ mice exhibited accelerated wound healing similar to healthy mice. These results demonstrate that loss of growth factors from saliva is associated with profoundly reduced oral wound healing, suggesting that therapeutic treatment with topical delivery may be beneficial to patients with type 1 diabetes and oral wound complications.

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Section: Discussionmentioning

confidence: 99%

Reduced Oral Wound Healing in the NOD Mouse Model for Type 1 Autoimmune Diabetes and Its Reversal by Epidermal Growth Factor Supplementation

Nagy

Nagashima²,

Cha³

et al. 2001

Diabetes

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“…C57BL/6 carrying either the NOD-derived genetic interval on chromosome 3 encompassing Idd3 , 10, 17, 18, or the Idd6 genetic intervals on chromosome 6 retained normal disease-free physiology. Conversely, NOD mice, containing chromosome regions of Hu et al ., 1992Hu and Humphreys-Beher, 1995;Humphreys-Beher et al ., 1993, 1994Kerr et al ., 1995;Yamamoto et al ., 1996Yamamoto et al ., , 1997Robinson et al ., 1996Robinson et al ., , 1997Robinson et al ., , 1998aRobinson et al ., , 1998bRobinson et al ., , 1998cYamachika et al ., 1998Yamachika et al ., , 2000Kong et al ., 1998a. c Konttinen et al ., 1994;Wu et al ., 1997. d Haneji et al ., 1997.…”

Section: (A) Geneticcontrol Of Autoimmunity Innod Mice Andhumanpatientsmentioning

confidence: 99%

Progress in Understanding Autoimmune Exocrinopathy Using the Non-obese Diabetic Mouse: An Update

Cha

Peck

Humphreys‐Beher

2002

Critical Reviews in Oral Biology & Medicine

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Sjögren's Syndrome (SS) is a chronic autoimmune disease characterized by histological and functional alterations of salivary and lacrimal glands that result in a severe dryness of the mouth and the eyes. The etiology of SS has remained undefined despite investigators' significant efforts to identify the mechanisms of initiation. Based on histopathology, several animal models are available-such as MRL/lpr, NZW/NZB, NFS/sld, graft vs. host, transgenic mouse expressing viral surface antigen, and the nonobese diabetic (NOD) mouse-for investigation of the etiology of SS. Biochemical and immunological similarities between human SS and autoimmune exocrinopathy (AEC) in the NOD mouse, including the loss of secretory function, establish the NOD mouse as an appropriate model to unravel the underlying pathophysiology of SS. Recently, several NOD congenic partner strains have been developed to investigate the roles of genetic intervals, cytokines, and autoantibodies in the disease pathogenesis. Studies on NOD-scid suggest that the pathogenesis of SS occurs in two phases: an asymptomatic phase, in which epithelial cells of exocrine tissues undergo dedifferentiation accompanied by elevated apoptosis; and a second phase in which autoaggression is mounted against target organ autoantigens, resulting in the activation of T-and B-cells, and the generation of autoantibodies. The presence of autoantibodies on the cell-surface signaling receptor, the muscarinic 3 receptor, in both SS patients and the NOD mice correlates with the hallmark clinical symptom of secretory dysfunction. Additionally, the NOD mouse model provides an important example of how both Th1 and Th2 cytokines, as well as non-immune genetic loci, are involved in the maintenance of and progression to the overt disease state. Ultimately, analysis of these data provides insight into potentially novel therapeutic interventions.

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“…30,32 The salivary glands produce and secrete a number of growth factors into saliva including EGF, NGF, TGFa, TGFb, insulin, IGF1 and IGF2. 34 In particular, NGF and EGF have been shown to stimulate the proliferation of salivary acinar cells. 35 In the animal model for Sjö gren's syndrome, the nonobese diabetic (NOD) mouse, reduced levels of insulin and IGF1 correlated with the onset of clinical symptoms, 34 suggesting that adequate IGF1 blood levels are required to maintain the viability of salivary acinar cells.…”

Section: Introductionmentioning

confidence: 99%

Synergistic suppression of apoptosis in salivary acinar cells by IGF1 and EGF

et al. 2003

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Tissue homeostasis requires balancing cell proliferation and programmed cell death. IGF1 significantly suppressed etoposide-induced apoptosis, measured by caspase 3 activation and quantitation of cellular subG 1 DNA content, in rat parotid salivary acinar cells (C5). Transduction of C5 cells with an adenovirus expressing a constitutively activated mutant of Akt-suppressed etoposide-induced apoptosis, whereas a kinase-inactive mutant of Akt suppressed the protective effect of IGF1. IGF1 also suppressed apoptosis induced by taxol and brefeldin A. EGF was unable to suppress apoptosis induced by etoposide, but was able to synergize with IGF1 to further suppress caspase 3 activation and DNA cleavage after etoposide treatment. The catalytic activity of Akt was significantly higher following stimulation with both growth factors compared to stimulation with IGF1 or EGF alone. These results suggest that a threshold of activated Akt is required for suppression of apoptosis and the cooperative action of growth factors in regulating salivary gland homeostasis.

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Detection of insulin and insulin-like growth factors I and II in saliva and potential synthesis in the salivary glands of mice

Cited by 64 publications

References 38 publications

Reduced Oral Wound Healing in the NOD Mouse Model for Type 1 Autoimmune Diabetes and Its Reversal by Epidermal Growth Factor Supplementation

Reduced Oral Wound Healing in the NOD Mouse Model for Type 1 Autoimmune Diabetes and Its Reversal by Epidermal Growth Factor Supplementation

Progress in Understanding Autoimmune Exocrinopathy Using the Non-obese Diabetic Mouse: An Update

Synergistic suppression of apoptosis in salivary acinar cells by IGF1 and EGF

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