Experimental reduction of B‐cell mass: Implications for the pathogenesis of diabetes

Weir, Gordon C.; Leahy, Jack L.; Bonner-Weir, Susan

doi:10.1002/dmr.5610020108

Cited by 141 publications

(105 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Nevertheless, after the 4 th month of life, 100% of the n5-STZ rats showed glycemic levels between 120 and 360 mg/dL, similar to the glycemic mean observed by other researchers 24,25 thus ensuring the viability of the model for mild diabetes induction. Further, Weir et al 26 demonstrated that n5-STZ rats presented lack of significant insulin re-accumulation in the pancreas, 2 weeks after the b-cell insult.…”

Section: Discussionmentioning

confidence: 99%

Neonatally-induced diabetes: lipid profile outcomes and oxidative stress status in adult rats

Sinzato¹,

Lima²,

Campos³

et al. 2009

Rev. Assoc. Med. Bras.

View full text Add to dashboard Cite

0.05) in the n5-STZ animals when compared to control group. However n5-STZ animals showed a significant decreased HDL-cholesterol rate (p<0.05). CONCLUSION: This streptozotocin-induced diabetes model in rats caused hyperglycemia (120-360mg/dL), characterizing mild diabetes. This glycemic level led to HDL-lipoprotein alteration, which was not sufficient to impair antioxidant enzyme activities or determination of lipid peroxidation in adult life of rats. Further this experimental investigation contributed to the understanding of different results found in other models for mild/moderate diabetes induction in laboratory animals as well as to a better comprehension of the pathophysiological mechanisms of mild diabetes or hyperglycemia in humans.]]>

show abstract

Section: Discussionmentioning

confidence: 99%

Neonatally-induced diabetes: lipid profile outcomes and oxidative stress status in adult rats

Sinzato¹,

Lima²,

Campos³

et al. 2009

Rev. Assoc. Med. Bras.

View full text Add to dashboard Cite

show abstract

“…It was demonstrated more than 20 years ago that the glycogen stores in Beta cells of hyperglycaemic rats are mobilized within 45 min of being exposed in vitro to a very low glucose concentration [27]. Second, the rapid reversability may explain the paradox whereby perfused pancreas studies in diabetic rat models have routinely shown loss of glucose-induced insulin output [28] whereas isolated islets from these same rats are normally glucose responsive [29][30][31]. The most likely explanation is that during the several hour isolation procedure Beta cells are no longer exposed to the same high glucose levels which occur in vivo, thereby allowing glucose-induced insulin secretion to revert to normal.…”

Section: Discussionmentioning

confidence: 99%

Beta-cell dysfunction in hyperglycaemic rat models: recovery of glucose-induced insulin secretion with lowering of the ambient glucose level

Leahy

Weir

1991

Diabetologia

Self Cite

View full text Add to dashboard Cite

Summary. Glucose-induced insulin secretion is lost in the face of chronic hyperglycaemia. The same defect is present when normal rats are made hyperglycaemic by 48-h glucose infusions. Insulin secretory responses were mapped out during the post-infusion period in order to determine how long it takes for normal Beta-cell function to recover, and to identify factors which influence the rate of recovery. Male Sprague Dawley rats weighing 200-250 g were infused with 50% glucose or 77 mmol/1 NaC1 for 48 h. The glucose-infused rats were mildly hypoglycaemic for 14 h after the infusion ceased. Glucose-induced insulin secretion, absent at the end of the glucose infusion, was normal 6 h post-infusion. Such rapid recovery was not because of the short duration of hyperglycaemia; mild hypoglycaemia from a 5-h insulin infusion in 90% pancreatectomized rats resulted in a four-fold rise in glucose-induced insulin secretion. Under in vitro conditions, extreme glucose deprivation caused by perfusing the pancreas of glucose-infused rats with buffer devoid of glucose restored glucose-induced insulin secretion in just 37 min. Therefore, the suppression of glucose-induced insulin release by chronic hyperglycaemia is a dynamic situation that requires ongoing hyperglycaemia to prevent the reappearance of glucose responsiveness. This study shows recovery of glucose-induced insulin secretion after just 6 h of mild hypoglycaemia in vivo and even faster recovery with more severe glucose deprivation in vitro. Our results suggest that there is an inverse relationship between the rate of return of Betacell glucose responsiveness and the ambient glucose concentration.Key words: Animal models, Type 2 (non-insulin-dependent) diabetes mellitus, insulin secretion, insulin treatment, hypoglycaemia, islets of Langerhans.Normally, the plasma glucose concentration exerts the dominant influence over insulin secretion. Type 2 (noninsulin-dependent) diabetes mellitus is characterized by Beta cells which no longer respond to a changing glucose level [1][2][3][4]. We have proposed that glucose-induced insulin secretion is lost as a direct result of Beta cells being exposed to a chronically elevated glucose concentration [4,5]. Support for this idea has come from animal studies in which normal rats made hyperglycaemic through a variety of mechanisms develop a similar defect [6.9], and also that normalizing the plasma glucose concentration in these rats with phloridzin restores glucose-induced insulin secretion [10,11].Little is known about reversal of secretory defects in non-insulin-dependent diabetes mellitus except that restoration of euglycaemia often results in the reappearance of glucose-induced insulin release [4, 12-14]. The recovery time has not been mapped out, nor has much been learned about what conditions speed up or retard recovery. Animal models should theoretically provide a way to investigate this question, but reversal studies in hyperglycaemic rat models have provided conflicting results. Using in vitro techniques, glucose-induced insuli...

show abstract

“…hyperglycaemia consequent to decreased beta-cell mass drives the impairment in beta-cell function. Distinguishing between the two is complicated by the fact that decreasing beta-cell mass experimentally more often than not leads to a more or less prolonged period of hyperglycaemia [55,56]. Moreover, in many instances there is a compensatory regeneration of beta cells.…”

Section: Mechanism Of Beta-cell Death In Type 2 Diabetesmentioning

confidence: 99%

Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications

Donath

Halban²

2004

Diabetologia

371

245

View full text Add to dashboard Cite

Increasing evidence indicates that decreased functional beta-cell mass is the hallmark of both Type 1 and Type 2 diabetes. This underlies the absolute or relative insulin insufficiency in both conditions. In this For Debate, we consider the possible mechanisms responsible for beta-cell death and impaired function and their relative contribution to insulin insufficiency in diabetes. Betacell apoptosis and impaired proliferation consequent to hyperglycaemia is one pathway that could be operating in all forms of diabetes. Autoimmunity and other routes to beta-cell death are also considered. Recognition of decreased functional beta-cell mass and its overlapping multifactorial aetiology in diabetic states, leads us to propose a unifying classification of diabetes. [Diabetologia (2004) 47:581-589]

show abstract

Experimental reduction of B‐cell mass: Implications for the pathogenesis of diabetes

Cited by 141 publications

References 110 publications

Neonatally-induced diabetes: lipid profile outcomes and oxidative stress status in adult rats

Neonatally-induced diabetes: lipid profile outcomes and oxidative stress status in adult rats

Beta-cell dysfunction in hyperglycaemic rat models: recovery of glucose-induced insulin secretion with lowering of the ambient glucose level

Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications

Contact Info

Product

Resources

About