The Third Phase of In Vitro Insulin Secretion: Evidence For Glucose Insensitivity

Bolaffi, Janice L.; Heldt, Anneliese; Lewis, Laurie; Grodsky, Gerold M.

doi:10.2337/diab.35.3.370

Cited by 77 publications

(44 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether such glucose effects are present in cultured islets is at present debated. Several reports suggest that so-called "glucose toxicity" can be observed in cultured rodent islets (8)(9)(10)(11), whereas we and others have been unable to observe such effects (12)(13)(14)(15)(16). These discrepancies may be explained by the use of different culture conditions and, most likely, by genetic differences between the strains of animals used (see reference 7).…”

Section: Introductionmentioning

confidence: 47%

Impairment of glucose-induced insulin secretion in human pancreatic islets transplanted to diabetic nude mice.

Jansson¹,

Eizirik²,

Pipeleers³

et al. 1995

J. Clin. Invest.

View full text Add to dashboard Cite

Hyperglycemia-induced ,8-cell dysfunction may be an important component in the pathogenesis of non-insulin-dependent diabetes mellitus. However, most available data in this field were obtained from rodent islets. To investigate the relevance of this hypothesis for human ,8-cells in vivo, human pancreatic islets were transplanted under the renal capsule of nude mice. Experimental groups were chosen so that grafted islets were exposed to either hyper-or normoglycemia or combinations of these for 4 or 6 wk. Grafts of normoglycemic recipients responded with an increased insulin release to a glucose stimulus during perfusion, whereas grafts of hyperglycemic recipients failed to respond to glucose. The insulin content of the grafts in the latter groups was only 10% of those observed in controls. Recipients initially hyperglycemic (4 wk), followed by 2 wk of normoglycemia regained a normal graft insulin content, but a decreased insulin response to glucose remained. No ultrastructural signs of 13-cell damage were observed, with the exception of increased glycogen deposits in animals hyperglycemic at the time of killing. It is concluded that prolonged exposure to a diabetic environment induces a long-term secretory defect in human 13-cells, which is not dependent on the size of the islet insulin stores. (J. Clin. Invest. 1995. 96:721-726.)

show abstract

Section: Introductionmentioning

confidence: 47%

Impairment of glucose-induced insulin secretion in human pancreatic islets transplanted to diabetic nude mice.

Jansson¹,

Eizirik²,

Pipeleers³

et al. 1995

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…While this increase is small, the possibility should be considered that such increases may initiate a vicious cycle of hyperglycemia, pancreatic refractoriness to glucose, and further hyperglycemia (65)(66)(67). If such were the case, it might help to explain the effect of duration of obesity on the incidence of diabetes (68).…”

Section: Resultsmentioning

confidence: 99%

Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man.

Lillioja¹,

Young²,

Culter³

et al. 1987

J. Clin. Invest.

722

484

View full text Add to dashboard Cite

We have compared the capillary density and muscle fiber type of musculus vastus lateralis with in vivo insulin action determined by the euglycemic clamp (M value) in 23 Caucasians and 41 Pima Indian nondiabetic men. M value was significantly correlated with capillary density (r = 0.63; P < 0.0001), percent type I fibers (r = 0.29; P < 0.02), and percent type 2B fibers (r = -0.38; P < 0.003). Fasting plasma glucose and insulin concentrations were significantly negatively correlated with capillary density (r = -0.46, P . 0.0001; r = -0.47, P . 0.0001, respectively). Waist circumference/thigh circumference ratio was correlated with percent type 1 fibers (r = -039; P < 0.002). These results suggest that diffusion distance from capillary to muscle cells or some associated biochemical change, and fiber type, could play a role in determining in vivo insulin action. The association of muscle fiber type with body fat distribution may indicate that central obesity is only one aspect of a more generalized metabolic syndrome. The data may provide at least a partial explanation for the insulin resistance associated with obesity and for the altered kinetics of insulin action in the obese.

show abstract

“…This could not be attributed to any significant reduction in insulin content of the pancreas, suggesting a lesion not in biosynthesis but in signal transduction. Additionally, Grodsky and Bolaffi probed the evolution of the secretory effect in more detail and the term "third phase," which is after the biphasic pattern, was applied to the reduced secretion that accompanied sustained glycemic stimulation (33,34,(61)(62)(63). Their results suggest that signal generation plays an important role in ␤-cell desensitization.…”

Section: ␤-Cell Desensitizationmentioning

confidence: 99%

Physiologic Implications of Phosphoinositides and Phospholipase C in the Regulation of Insulin Secretion

Yamazaki

Zawalich

2010

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

View full text Add to dashboard Cite

SummaryThe secretion of insulin from the pancreatic ␤ -cell must be commensurate to satisfy the insulin requirements of the organism. This cell has a great flexibility to meet these requirements which are increased not only by the ingestion of nutrients (increase of plasma glucose) but also by the sensitivity of target tissues to insulin as well. The insulin secretion is a complex biochemical event regulated by a host of potential second messenger molecules acting alone or in concert. These events include the cation calcium, which gains access to the ␤ -cell via the opening of voltage-regulated channels, cAMP and phosphoinositidederived second messenger molecules, generated as a consequence of phospholipase C (PLC) activation. In this review, we focused on phosphoinositides, PLC/Phosphokinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) cascade in the regulation of insulin secretion. We also described our studies on the mechanism of the ␤ -cell desensitization using perifused islets. It is suggested that a failure of the signaling events contribute to the pathogenesis of diabetes in which the ␤ -cell can no longer secrete the required amounts of insulin. It has been observed that chronic exposure to high glucose desensitizes the ␤ -cells to subsequent stimulation. We suggested that the failure of PLC activation can be attributed in the impairment of insulin secretion by chronic sustained glucose exposure. It may contribute to the vicious circle of impaired insulin secretion leading up to diabetes.

show abstract

The Third Phase of In Vitro Insulin Secretion: Evidence For Glucose Insensitivity

Cited by 77 publications

References 13 publications

Impairment of glucose-induced insulin secretion in human pancreatic islets transplanted to diabetic nude mice.

Impairment of glucose-induced insulin secretion in human pancreatic islets transplanted to diabetic nude mice.

Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man.

Physiologic Implications of Phosphoinositides and Phospholipase C in the Regulation of Insulin Secretion

Contact Info

Product

Resources

About