First phase insulin release in the non-obese diabetic mouse: correlation with insulitis, beta cell number and autoantibodies

Reddy, Shiva; Liu, W.; Thompson, Jessica; Bibby, N.J.; Elliott, Robert B.

doi:10.1016/0168-8227(92)90039-t

Cited by 15 publications

(12 citation statements)

References 36 publications

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“…Similar to what has been reported in human beings, a significant decrease in FPIR during an intraperitoneal glucose tolerance test has been observed in NOD mice despite maintenance of glucose tolerance during the pre-diabetic period [7]. Previously, Reddy and colleague demonstrated a decrease in FPIR in vivo when comparing female NOD mice at 6 weeks and a second cohort at 21 weeks of age [40]. Two additional groups reported reductions in FPIR by pancreas perfusion between 23 and 32, as well as 8 and 18 weeks of age, respectively [7; 8].…”

Section: Nod Mouse Modelsupporting

confidence: 66%

Metabolic Abnormalities in the Pathogenesis of Type 1 Diabetes

Zheng

Mathews

2014

Curr Diab Rep

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Clinical onset of Type 1 Diabetes (T1D) is thought to result from a combination of overt beta cell loss and beta cell dysfunction. However, our understanding of how beta cell metabolic abnormalities arise during the pathogenesis of disease remains incomplete. Despite extensive research on the autoimmune nature of T1D, questions remain regarding the time frame and nature of beta cell destruction and dysfunction. This review focuses on the characterizations of beta cell dysfunction in the pre-diabetic and T1D human and mouse model. Studies have shown evidence supporting progressive loss of beta cell mass and function prior to T1D onset, while other scientists argue beta cell destruction occurs later in the disease process. Determining the time frame of beta cell destruction and identifying metabolic mechanisms that drive beta cell dysfunction has high potential for successful interventions to maintain insulin secretion for individuals with established T1D as well as those with pre-diabetes.

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Section: Nod Mouse Modelsupporting

confidence: 66%

Metabolic Abnormalities in the Pathogenesis of Type 1 Diabetes

Zheng

Mathews

2014

Curr Diab Rep

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“…In these studies, increased fasting glucose and loss of FPIR was associated with the degree of insulitis. In cross-sectional studies using intravenous glucose tolerance test, Reddy et al (11) showed an age-related progressive decline in FPIR to glucose. In another cross-sectional study using in situ pancreas perfusion, Sreenan et al (12) reported progressive decreases in glucose- and arginine-stimulated insulin secretion in NOD females at 8, 13, and 18 weeks of age.…”

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confidence: 99%

Progressive Erosion of β-Cell Function Precedes the Onset of Hyperglycemia in the NOD Mouse Model of Type 1 Diabetes

et al. 2011

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OBJECTIVEA progressive decline in insulin responses to glucose was noted in individuals before the onset of type 1 diabetes. We determined whether such abnormalities occurred in prediabetic NOD mice—the prototypic model for human type 1 diabetes.RESEARCH DESIGN AND METHODSMorning blood glucose was measured every other day in a cohort of NOD females. Glucose tolerance and insulin secretion were measured longitudinally by intraperitoneal glucose tolerance tests in NOD/ShiLtJ and BALB/cJ mice 6 to 14 weeks of age. Arginine-stimulated insulin secretion and insulin sensitivity were assessed during intraperitoneal arginine or intraperitoneal insulin tolerance tests.RESULTSDuring prediabetes, NOD females displayed a progressive increase in glucose levels followed by an acute onset of hyperglycemia. First-phase insulin responses (FPIRs) during the intraperitoneal glucose tolerance test (IPGTT) declined before loss of glucose tolerance in NOD. The failure of FPIR could be detected, with a decline in peak insulin secretion during IPGTT. Arginine-stimulated insulin secretion remained unchanged during the study period. The decline in insulin secretion in NOD mice could not be explained by changes in insulin sensitivity.CONCLUSIONSThere was an impressive decline in FPIR before changes in glucose tolerance, suggesting that impairment of FPIR is an early in vivo marker of progressive β-cell failure in NOD mice and human type 1 diabetes. We portend that these phenotypes in NOD mice follow a similar pattern to those seen in humans with type 1 diabetes and validate, in a novel way, the importance of this animal model for studies of this disease.

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“…For glucose tolerance determinations, overnight-fasted mice were injected ip with glucose (Assistance Publique, Paris, France), dissolved in 0.9% NaCl, at doses varying from 1-6 g/kg (19,20,22,25,26). For basal and glucose tolerance test determinations, all experiments started at 0900 h. In all cases, unanesthetized animals were bled in less than 2 min by retroorbital puncture.…”

Section: Experimental Protocol Under Basal Conditions and For Glucosementioning

confidence: 99%

“…In line with the possible existence of hyperactive ␤-cells at the prediabetic stage in humans, the following have been observed: 1) increased levels of insulin and proinsulin under basal fasting conditions in nondiabetic identical twins of IDDM patients (5, 6); and 2) increased levels of proinsulin under basal conditions and after glucose stimulation in first-degree relatives or newly diagnosed patients (3, 9 -14). In spontaneous experimental models of IDDM, most data dealing with glucose homeostasis at the prediabetic stage demonstrated a lower insulin response to glucose in both BB rats (15-21) and NOD mice (22)(23)(24)(25)(26). However, in the BB rat in particular, the existence of hyperactive ␤-cells at the prediabetic stage can be suggested on the basis of the following findings: 1) hyperinsulinemia in some rats before the onset of diabetes (19); and 2) enhanced in vitro ␤-cell sensitivity to glucose in inflamed islets, but not normal islets, from nondiabetic BB rats (27).…”

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confidence: 99%

Glucose Homeostasis in the Nonobese Diabetic Mouse at the Prediabetic Stage¹

et al. 1998

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Because few data were available on glucose homeostasis at the early prediabetic stage in the nonobese diabetic (NOD) mouse, we investigated glycemia, insulinemia, and pancreatic insulin content under basal conditions in both sexes of 4-, 6-, and 8-week-old fed NOD mice, compared with sex-and age-matched fed C57BL/6 mice. We also investigated glucose tolerance in both sexes of fasting 8-week-old NOD and C57BL/6 mice. The main results obtained under basal fed conditions, when comparing both strains, were lower glycemia and higher insulinemia in NOD females at all ages investigated and in NOD males (particularly at 6 weeks of age). Glucose tolerance tests showed that: 1) the blood glucose response to 1 g/kg ip glucose was less sustained in both sexes of 8-week-old NOD mice than in their control counterparts; 2) the blood insulin response to glucose (1 g/kg ip) appeared earlier in both sexes of NOD mice than in sex-matched C57BL/6 mice; 3) an unusual sexual dimorphism existed in NOD mice, compared with controls, with females secreting, in response to glucose, twice as much insulin as males; 4) dose-response studies (1-6 g/kg glucose) confirmed the lower increase in blood glucose levels in both sexes of NOD mice and their unusual sexual dimorphism in insulin secretion; and 5) glucose tolerance tests in 4-to 8-week-old NOD mice showed that although the sexual dimorphism in insulin secretion was not observed in 4-week-old mice, it was particularly striking at 6 weeks of age. Taken together, these results suggest that ␤-cell hyperactivity exists in the NOD mouse at the early prediabetic stage, especially in NOD females. (Endocrinology 139: [1115][1116][1117][1118][1119][1120][1121][1122][1123][1124] 1998) I NSULIN-DEPENDENT diabetes mellitus (IDDM), or type 1 diabetes, has a long prodromic phase in both humans (in whom the detection of autoantibodies precedes diabetes onset by years) and spontaneous models of the disease, such as the nonobese diabetic (NOD) mouse (in which insulitis precedes hyperglycemia by weeks or months) (1, 2). In firstdegree relatives of IDDM patients, with regard to glucose homeostasis, data vary from normal to subnormal or, even more surprisingly, to excessive insulin and C-peptide secretion in response to glucose and/or arginine (1-8). In line with the possible existence of hyperactive ␤-cells at the prediabetic stage in humans, the following have been observed: 1) increased levels of insulin and proinsulin under basal fasting conditions in nondiabetic identical twins of IDDM patients (5, 6); and 2) increased levels of proinsulin under basal conditions and after glucose stimulation in first-degree relatives or newly diagnosed patients (3, 9 -14). In spontaneous experimental models of IDDM, most data dealing with glucose homeostasis at the prediabetic stage demonstrated a lower insulin response to glucose in both BB rats (15-21) and NOD mice (22)(23)(24)(25)(26). However, in the BB rat in particular, the existence of hyperactive ␤-cells at the prediabetic stage can be suggested on the...

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First phase insulin release in the non-obese diabetic mouse: correlation with insulitis, beta cell number and autoantibodies

Cited by 15 publications

References 36 publications

Metabolic Abnormalities in the Pathogenesis of Type 1 Diabetes

Metabolic Abnormalities in the Pathogenesis of Type 1 Diabetes

Progressive Erosion of β-Cell Function Precedes the Onset of Hyperglycemia in the NOD Mouse Model of Type 1 Diabetes

Glucose Homeostasis in the Nonobese Diabetic Mouse at the Prediabetic Stage¹

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First phase insulin release in the non-obese diabetic mouse: correlation with insulitis, beta cell number and autoantibodies

Cited by 15 publications

References 36 publications

Metabolic Abnormalities in the Pathogenesis of Type 1 Diabetes

Metabolic Abnormalities in the Pathogenesis of Type 1 Diabetes

Progressive Erosion of β-Cell Function Precedes the Onset of Hyperglycemia in the NOD Mouse Model of Type 1 Diabetes

Glucose Homeostasis in the Nonobese Diabetic Mouse at the Prediabetic Stage1

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Glucose Homeostasis in the Nonobese Diabetic Mouse at the Prediabetic Stage¹